A team of researchers led by a University of Louisville experimental neuropathologist has discovered important characteristics of certain types of brain tumors that may lead to novel options to treat them and better understanding of how they and other brain tumors arise.

Norman Lehman, UofL professor of pathology and biochemistry and molecular genetics, led the study of the origins of uncommon brain tumors called astroblastomas that most often affect children and young adults.

“This research gives us a new understanding of how childhood brain tumors with origins in early embryonic development arise,” Lehman said. “It could lead to detection very early in the formation of these types of tumors, new treatments or potentially even strategies to prevent their formation.”

The research, published this week in Nature Communications, revealed two distinct subtypes of these tumors, one that develops in early childhood, the other developing later in life.

The type of astroblastoma that occurs in young children is derived from radial glia that arise very early in the embryonic brain and are biologically related to tumors known as ependymomas. The other type of astroblastoma, typically occurring in young adults, is derived from later neural stem cells called outer radial glia and are biologically related to astrocytomas.

The research also has implications in understanding differences in tumor occurrence based on sex.

“The early-development astroblastoma tumor appears to occur exclusively in females, which may give us a better understanding of why certain types of tumors not involving the reproductive system are found more frequently in males or females,” Lehman said.

Lehman also said the tumors’ mechanisms likely involve alterations in DNA methylation that could possibly be exploited to detect tumor development early on or mitigate their development, but also are associated with other types of neural conditions.

“The altered genes that are associated with the development of these tumors are genes that also are associated with developmental neurocognitive disorders such as autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia,” he said.

Contributors to the work included Brian Williams and Akshitkumar Mistry, both assistant professors in the UofL Department of Neurological Surgery and neurosurgeons with UofL Health, UofL biochemistry and molecular genetics graduate student Müge Sak and former UofL pathology resident Khaled Alkhateeb.

“We have very few treatments for brain tumors,” Mistry said. “If we can get to the bottom of this very rare brain tumor in terms of its biological origins or its biological behavior, then that knowledge could be applied to some of the other aggressive brain cancers. The question is, how does this sort of research apply to other tumors that are not well understood, and can we gain insight into those other tumors to hopefully figure out how they’re behaving?”

Other important contributors included developmental biologist Nathalie Spassky of the Institut de Biologie de l’École Normale Supérieure in Paris and Kenneth Aldape of the National Cancer Institute Center for Cancer Research. 

Central High School went red on Monday, April 18, as part of a UofL Takeover where 11^th graders  gathered in-person  to speak with members of the UofL community about programs offered at the university and to how to succeed long-term. The event offered students the opportunity to engage with a panel of UofL speakers as well as participate in a college fair expo. In addition to the School of Medicine, the event was attended by the UofL Admissions, SPEED School, Nursing and other programs.

“The UofL Day at Central High School provides students with a face-to-face opportunity to gain insight about internships, co-ops, research, and shadowing experiences available to them,” said Dwayne Compton, Chief Diversity Officer for UofL School of Medicine. “Early exposure to career pathway initiatives offered by UofL assist with closing the opportunity gaps we know exist. Now more than ever, it is vital that UofL collaborate with JCPS schools like Central to assist students with becoming college and career ready.”

Panelists of the event included representatives from Dentistry, Nursing, Public Health, Admissions, and Medicine. The ULSOM panelists answered a variety of questions from the audience, including scholarship opportunities and challenges they faced during their careers. ULSOM asked panelists why the UofL day at Central is so important to high school students.

“I think it’s important to learn in the beginning what the trajectory is to go into medicine,” said Bill Ngha, Pediatrics Resident Physician, “They’ll need to know what courses they’ll have to take and how to invest in yourself early on.”

Central high school has six magnet programs in which students can elect to participate in beginning their freshman year. Dennis Mostiller and Emmanuel Edwards are two students participating in the Pre-Medicine program that is a part of the Medical/Health Services magnet. Motivated by television shows such as Grey’s Anatomy and the hands-on activities, they’re confident Medicine is the program for them.

The Pre-Medicine Program at Central High School is led by Shantel Reed, pre-medicine magnet teacher. She works to  capitalize on her student’s interests to increase engagement and success. “On Fridays, our classes watch an episode of Grey’s Anatomy as an assignment,” said Reed, “They pair medical terms from the show with their coursework to make connections.”

The importance of the Pre-Medicine program at Central High School was affirmed by UofL Pediatrics Attending, Jennifer Porter. “We know that we need diversity in medicine; patients do better with physicians who look like them. It’s important that we invest here in Kentucky to recruit people to stay here, too.”

The UofL Day at Central is part of a collaborative partnership that began in 2018 between the University of Louisville Office of Diversity and Community Engagement and Central High School. Each year more than 120 students from Central participate in the magnet programs and are introduced to UofL programming that support diversity in medicine and other concentration areas. The Pre-Medicine program traditionally graduates 33 students each year.

“The School of Medicine has a vested interest in the success of our area high school students. Our partnership with Central High School and other magnet programs is vital to our success in caring for our community through a diverse future workforce,” said Toni Ganzel, dean of the School of Medicine.

View photos from the event here. 

The University of Louisville Christina Lee Brown Envirome Institute has launched a monthly podcast, “Elements of Nature,” to increase listeners’ understanding of the connections between nature and health.

In each episode, Aruni Bhatnagar, director of the Envirome Institute and chief of the UofL Division of Environmental Medicine, hosts an expert to discuss how natural forces – water, air, fire and space – affect human health and wellness. Bhatnagar and his guests discuss topics such as how sleep and sunlight regulate our mood and fitness, how air pollution impairs health and increases the risk of chronic disease or how greenspaces and vegetation affect attention and immunity.

“This podcast, ’Elements of Nature,’ is a monthly series about how natural forces shape and influence us and, if we pay attention, how we can live a more gratifying, healthy and harmonious life,” Bhatnagar said. “We’ve talked with renowned scientists, professors, authors and thought leaders about our relationship with elements of nature and how it impacts our health and resilience.”

In the first episode of “Elements of Nature,” Bhatnagar and guest Russell Foster, a professor of circadian neuroscience at the University of Oxford, discuss how circadian rhythms, light and sleep affect our wellbeing and performance. Future topics on “Elements of Nature” consider health effects of air pollution, the level of greenness in residential areas and the importance of the sun.

“Elements of Nature” is available on Apple, Google, Spotify, Stitcher and other podcast platforms.

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 Upcoming episodes of “Elements of Nature”:

#2 Dr. Arden Pope – Air (April)

C. Arden Pope III, PhD, is an American professor of economics at Brigham Young University and one of the world's foremost experts in environmental science.

#3 Gay Browne – Green (May)

Gay Browne is an environmental advocate and humanitarian, the founder of Greenopia, a comprehensive guide to help consumers positively impact their personal health, and author of “Living with a Green Heart.”

#4 Dr. Michael Holick – Sun (June)

Michael F. Holick, PhD, MD, is professor of medicine, physiology and biophysics, director of the General Clinical Research Unit, director of the Bone Health Care Clinic and director of the Heliotherapy, Light and Skin Research Center at Boston University Medical Center.

#5 Richard Louv – Nature (July)

Richard Louv is an American non-fiction author and journalist best known for his seventh book, “Last Child in the Woods: Saving Our Children from Nature-Deficit Disorder,” which investigates the relationship of children and the natural world in current and historical contexts.

Staff members from the University of Louisville School of Medicine were recognized for their creativity and dedication at the 6^th annual Dean’s Staff Excellence Awards on March 31.

The event, hosted by Dean Toni Ganzel, honored School of Medicine Staff nominated by their colleagues for their outstanding excellence exhibited over the last 12 months.

“Our staff lean in during periods of plenty and during periods of challenge, and let’s face it: we see a little more periods of challenge than we do periods of plenty, especially the last two years,” said Dean Ganzel, speaking during the event. “You are sometimes sung, sometimes unsung heroes in just the way that you quietly and daily carry out exemplary work.”

Over 30 staff members were nominated for seven different award categories. The awards were presented to:

• Shelly Matthis and Rhonda Pugh, co-awardees for Performance Excellence in an Administrative Office
• Jason Xu, for Performance Excellence in a Clinical Department
• Phyllis Harris, for Heart of the School
• Shorye Durrett, for the Anti-Racism, Diversity, Equity, and Inclusion Award
• Medical Student Affairs, for Team of the Year
• Mandy Ryan, for Employee of the Year
• Ashlee Melendez, for the Dean’s Lifetime Achievement Award

This was the first in-person award ceremony in two years due to the COVID-19 pandemic.

“It was so nice to see everybody face-to-face and in person,” said Dean Ganzel, “I wish we could have these monthly.”

View photos from the event here.

Lack of mentorship and exposure to the medical field is often a barrier for Black and Brown students interested in becoming doctors, but UofL is working to change that through the Porter Scholars in Medicine Program.

“The road to becoming a doctor is a long and often bumpy one for everyone. Having a community to support a student and provide guidance can make the difference between wearing a white coat and giving up on that dream,” said Brit Anderson, a physician in UofL’s Department of Pediatrics. “Students who do not have family and friends in the medical field may miss out on this supportive medical community.”

Anderson, along with V. Faye Jones, associate vice president for health affairs – diversity initiatives at the Health Sciences Center and vice chair of inclusive excellence in the Department of Pediatrics, teamed up with Leondra Gully, advisor for the Woodford R. Porter Scholarship Program, to create the new initiative.

The program is aimed at UofL’s Porter Scholars, a scholarship program for exceptional undergraduate students of color from Kentucky and neighboring Indiana counties. First-year students through seniors interested in health care go through an application process to take part in the niche Porter Scholars in Medicine Program, now in its second year.  

Students receive mentoring and shadowing experiences from UofL physicians, and are also able to participate in clinical experiences including simulation and ultrasound. They learn about the medical school application process and entrance exam, gain insight related to the history of medical disparities in underrepresented communities and connect with students in UofL’s chapter of the Student National Medical Association. The program also hosts book clubs and discussions.

“I don’t think people realize the value of this program; there were no specific programs for Black and Brown students wanting to go into medicine. This a welcome space, and a different feeling of support – it’s what we need,” said Hayley Benson, a biology major and one of 17 students participating in this year’s Porter Scholars in Medicine program.

Diversifying the medical field

Gully says the program not only supports students interested in becoming physicians, but the ultimate outcome is far reaching – to diversify the medical field.

“We know from life experiences and the literature more diverse doctors are needed,” she said. “Diversity in the medical field has been proven to impact health disparities for marginalized communities and goes a long way in helping those communities receive equitable health care and improve patient outcomes.”

Senior Diane Appiasie can relate. She says her interest in medicine stems from the impact of health care providers throughout her life, and the aspiration to provide the same quality of care for others.

“I have been further driven to pursue a career in the medical field by a desire to continue advocating for health equity as a health care professional,” says Appiasie, who hopes to focus on a career in emergency medicine and neurology.

One future goal of the program is to engage students in off-campus experiences. Gully and her team are working to coordinate an opportunity this fall for Porter Scholars to see a live surgery through the Kentucky Science Center Pulse of Surgery program. Organizers also hope to explore ways to eventually secure funding for students who want to attend medical school.

“We know this program can be impactful, and we’re excited to see it grow,” Anderson said. “It is such an honor to work with this team and meet these wonderful students as we strive to advance health equity in our community.”

When Keith Smith recently got a new tablet, it wasn’t for watching videos or scanning social media.

Instead, this tablet allows Smith, who has tetraplegia, more independent control of an implanted Medtronic Intellis™ neurostimulator, allowing him to better take advantage of the stimulator’s benefits for the disabling effects of a spinal cord injury.

Smith received the stimulator two years ago while participating in a study involving individuals paralyzed by spinal cord injuries at the University of Louisville’s Kentucky Spinal Cord Injury Research Center (KSCIRC). The stimulator has provided Smith benefits such as voluntary movement, increased trunk control and improved blood pressure regulation. 

“The stimulator has restored my health in a big way. I don’t feel sick all the time anymore. I’m not passing out; I’m not dizzy,” he said. “I am enjoying my life again. It gives me something I can use to fight for my recovery.”

To fully take advantage of the stimulator’s benefits, the stimulator must be adjusted periodically throughout the day to regulate his blood pressure and other functions, each of which requires distinct stimulator settings. Smith, who has limited use of his hands due to a C4-level spinal cord injury, previously had to rely on a caregiver to change the settings due to the small size of the buttons on the standard stimulator controller device.

But now, thanks to the new tablet controller with a larger, touch-screen interface designed with his needs in mind, Smith can adjust settings himself.

“Previously, the remote was controlled by my caregiver. I couldn’t do it because I don’t have [full use of] my hands. Now that we have this new technology, I can control it on my own,” Smith said. “I am going to be able to use many more functions and be able to control it and adjust it in a much more significant manner on my own. It’s a big benefit to my life.”

In addition to a more accessible interface, the updated controller has the capacity to store more setting configurations for immediate use and provides smoother transitions between configurations that allow the person with spinal cord injury to change positions such as from sitting to standing.

Over the last few months, the new tablet controllers have been provided to 16 participants in the spinal cord epidural stimulation research program at UofL. Additional participants will receive the new tablet controllers in the coming months, as well as any new participants receiving epidural stimulators.

Epidural stimulation, an experimental therapy for spinal cord injury recovery, involves implanting an electrode on the lower spinal cord, along with a neurostimulator under the patient’s skin, which delivers mild electrical impulses to the spine. When electrical pulses are delivered in different configurations, research at UofL and other centers has shown they help paralyzed individuals like Smith achieve voluntary movement, blood pressure regulation, the ability to stand, improvements in bowel, bladder and sexual function and other benefits, particularly when combined with activity-based therapy. Some participants even have been able to take steps.

UofL first used Medtronic epidural stimulators for spinal cord injury research in 2009 under an FDA Investigational Device Exemption. The research, led by Susan Harkema, professor of neurological surgery and associate director for KSCIRC, has resulted in multiple health benefits and function recovery for paralyzed individuals. While epidural stimulators, also known as spinal cord stimulators, have been proven to provide effective relief for chronic pain and are commercially available for this application, their use for individuals with spinal cord injury remains experimental.

The new controller, known as Stim X Release 1, also offers added benefits for the researchers by precisely recording stimulation use by the participants outside the lab.

“This is Release 1 and we expect future releases to continue to improve the technology,” said Claudia Angeli, assistant professor of bioengineering at UofL’s J.B. Speed School of Engineering and director of the Epidural Stimulation Program at KSCIRC. “Additional improvements are planned with feedback from the participants and the development of wireless sensors to monitor the user’s condition and adjust stimulator settings as needed. In a closed-loop or human-in-the-loop system, the controller could alert the user or adjust the stimulation based on a change in blood pressure, for example.”

UofL, Kessler Foundation, Medtronic, Johns Hopkins Applied Physics Laboratory and multiple funders are working together to fast-track technology improvements that allow individuals with spinal cord injury to realize the benefits of epidural stimulation in their homes and communities, not just in the research setting.

“This is the sort of innovation a Carnegie Research-1 university can and ought to be doing,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “This is innovation with real, human impact – work that advances health and helps people live lives that are healthier, more resilient and more fully empowered.”

This work is funded through the NIH BRAIN Initiative by the National Institute of Neurological Disorders and Stroke, the National Institutes of Health SPARC Common Fund Program, Kessler Foundation and the University of Louisville.

A new consortium of four Kentucky health care organizations, led by the University of Louisville School of Medicine, is working to connect a wide range of health care professionals and employers to better address workforce shortages in rural and underserved parts of the Commonwealth.

The Kentucky 3RNET Consortium — which also includes the Kentucky Office of Rural Health (KORH), the Kentucky Primary Care Association (KPCA) and the Kentucky Rural Health Association (KRHA) — will maintain and promote Kentucky-specific health care job postings on The National Rural Recruitment and Retention Network (3RNET), a nonprofit online portal that helps job candidates more easily find health care openings in rural and underserved communities and helps community health centers, critical access hospitals and rural health clinics recruit candidates for open positions.

Consortium members will jointly manage Kentucky’s presence on the 3RNET site to expand the types of jobs posted and increase the use of the service throughout the Commonwealth among both employers and candidates seeking jobs. This is the first time that a state’s postings at the 3RNET site will be monitored and maintained by a group of partners.

“Our Commonwealth faces significant health care personnel challenges. This new consortium leverages the unique perspective and expertise of each organization to engage with job seekers and employers,” said Brent Wright, associate dean for rural health innovation at the University of Louisville School of Medicine and the brainchild behind the consortium. “If we can fill vacancies in multiple health disciplines, we will improve access to health care services throughout the state.”

KORH Director Ernie Scott said bringing the four organizations together to collectively address health care workforce shortages in Kentucky communities makes perfect sense.

“Workforce shortages cannot be singlehandedly addressed by just one organization in Kentucky or any other state. Instead, we’ve got to take a ‘village’ approach — we’ve got to come together as a unified team with a unified purpose,” he said. “Working together, this consortium will allow us to have a greater impact than any of our organizations could have individually.”

Ashley Gibson, KPCA’s workforce program director, called the collaboration between organizations “essential” for the recruitment and retention of employees.

“Workforce shortages in our state are making it harder for people in many communities to access care,” she said. “This collaboration hopes to reverse that trend and actually expand access to health care services.”

KRHA Executive Director Tina McCormick said her organization is always looking for ways to support its members and partner with organizations that have a similar mission.

“Access to care is vital and without the workforce to support that care, our rural areas get left out again,” she said. “We hope with this partnership we will build strong bonds across the state to provide job seekers access to open positions and provide employers a mechanism to locate prospective employees for their vacancies.”

3RNET, which works at the national level to improve rural and underserved communities’ access to quality health care through the recruitment of physicians and other health care professionals, allows health care facilities to post their open positions online at 3rnet.org and lets health care professionals conduct free searches of those job openings. State-specific pages on the website — which contain information about communities, available job opportunities and loan repayment programs — are maintained by 3RNET members, including the newly formed Kentucky 3RNET Consortium.

A nationally renowned cardiologist and health equity expert has been selected to head the University of Louisville Department of Medicine. Kim Williams Sr. will serve as chair of the department beginning July 1.

As chair, Williams will lead the scientific, clinical and educational programs of the UofL School of Medicine’s largest department, which includes more than 200 faculty and 150 staff in 10 divisions. He will build collaborations within the School of Medicine and with its partners. He also will be responsible for the planning and guidance of clinical efforts within the UofL Health system as well as developing and implementing a vision for the department that integrates clinical, educational and research missions, while fostering a culture of collaboration, equity and inclusion.

“We are excited for Dr. Williams to be joining our team,” said School of Medicine Dean Toni Ganzel. “He brings a wealth of expertise in cardiology and health equity. His academic background, clinical experience and leadership skills will be strong assets to the department, the institution and our community. His work will enhance and augment our work with strategic partners in health equity.”

A Chicago native, Williams has over 40 years of experience as an educator, researcher, and clinician focused on advocacy for nutrition, national and international health care disparities, health care delivery and advanced access to cardiac imaging. He currently is chief of the Division of Cardiology at Rush University and associate dean for faculty diversity, equity and inclusion. He specializes in cardiology, cardio-nutrition, cardio-rheumatology, cardio-nephrology, preventive cardiology and cardiovascular radiology. A past president of the American College of Cardiology and the American Society of Nuclear Cardiology, he is former chairman of the board of directors of the Association of Black Cardiologists.

He also is the founder of the Urban Cardiology Initiative in Detroit, a program that works to reduce ethnic heart care disparities. Williams continues community-based efforts in Chicago at Rush, including leading the H.E.A.R.T. program (Helping Everyone Assess Risk Today), screening for heart disease and intervening with education, nutrition and lifestyle changes.

Williams earned his medical degree from the University of Chicago Pritzker School of Medicine. He completed his internship and residency at Emory University Department of Medicine and a fellowship in cardiology at the University of Chicago.

“Building and leading Rush cardiology has been challenging and fulfilling, yet I was drawn to the UofL Department of Medicine by the leaders, the faculty and the fundamentals already in place, as well as the potential that I see for growth and impact in the areas of prevention and health equity,” Williams said. “We have leadership with vision, and we have some existing programs that will be enhanced – and some robust opportunities to develop – aiming to expand health care access in Louisville, maintain our high level of clinical quality and patient experience, deliver cost efficient care and keep provider wellness at the forefront.”

Cognitive behavioral therapy is a highly effective treatment for depression. A number of factors can prevent patients from receiving successful therapy, however. The need for frequent visits – often more than once per week – taking time off work, transportation, the cost of visits or even access to providers trained in this therapy can prevent patients from getting treatment for their depression.

A newly published clinical trial led by University of Louisville physicians has shown that a computer-assisted therapy can overcome these barriers while providing effective treatment for depression.

Jesse Wright, professor of psychiatry at UofL and director of the UofL Depression Center, documented treatment results for a diverse group of 175 adults for depression. The study, published in JAMA Network Open in February, showed that patients in a primary care setting who participated in CCBT reported significantly greater improvement in their depressive symptoms than those receiving treatment as usual.

“With modest amounts of telephone support from a clinician, CCBT was associated with greater improvement in depression, anxiety and quality of life than usual treatment in a diverse group of primary care patients. We were pleased to see that CCBT had more than double the remission and response rates as usual treatment,” Wright said.

“There has been a historical lack of effective care for depression in the primary care setting,” he said “Because this study population included people with lower income and lack of internet access, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings.”

Rather than requiring frequent office visits, patients can engage in CCBT online whenever their schedule allows and from the comfort of their home. A primary care provider can monitor and support the patient's progress, helping patients who may not desire or be able to see a psychologist or psychiatrist for their therapy.

“Particularly during the COVID pandemic, we have seen how limited appointments are for mental health services and the rise of telemedicine has led to increasing comfort with utilizing technology to support health, which makes computer-assisted cognitive behavioral therapy a great option,” said Laura Bishop, an associate professor and internal medicine-pediatrics physician at UofL and a co-author of the study.

In the study, CCBT participants used the nine-lesson computer program “Good Days Ahead,” along with as many as 12 weekly telephone support sessions with a master’s level therapist, along with the treatment usually provided by the primary care sites.

“I think this is a preferable option for younger patients who often are more comfortable with self-reflection and working through the CCBT on a computer rather than meeting face-to-face with a provider,” Bishop said. “We've seen more and more familiarity with wellness and meditation apps over the past few years that have paved the way for CCBT to be widely accepted.”

Wright began work on computer-assisted therapy in the 1990s and led the initial development of Good Days Ahead. In addition to depression, Wright said CCBT also could be adapted to treatment for obsessive-compulsive disorder (OCD), anxiety, eating disorders or other conditions.

Patients in the Louisville area can request use of Good Days Ahead through the UofL Depression Center.

Good Days Ahead is being reviewed by the U.S. Food and Drug Administration under a new protocol for certification of therapeutic computer programs.

Wright retains an equity interest in MindStreet, Inc., the company that now manages Good Days Ahead.

A professor of medicine and director of the internal medicine residency program in the UofL School of Medicine, Dr. Jennifer Koch is a member of the Gender Equity in Medicine (GEM) research group, a collaboration of medical educators from multiple universities working together to better understand the impact of gender bias in medical training.

In September, the American Medical Association, the AMA Women Physicians Section (WPS) and the AMA Foundation awarded a $10,000 grant to the group as part of the 2021 Joan F. Giambalvo Fund for the Advancement of Women research grants program.

The group received the grant for a multi-site longitudinal study aimed at understanding the combined impact of race, ethnicity and gender on women’s experiences in graduate medical education, also known as medical residency. UofL News talked to Koch about why this work is important and how it will help ensure quality medical care for all.

UofL News: What have you and the group learned in your study of gender bias in graduate medical education?

Jennifer Koch: We have learned that there are differences based on gender in the assessment of learners (resident doctors) in internal medicine residency. Whereas residents who are men tend to receive performance scores that increase throughout their training as they gain experience, women residents are more likely to see a plateau in the performance scores they receive when they reach the halfway point in residency.

There is evidence that women doctors who are out in practice have better patient outcomes, which suggests that it is highly unlikely that the differences in assessment scores during residency represent a true difference in their performance during training. Therefore, this difference likely indicates the presence of gender bias in the educational experience of women residents.

ULN: What might the implications be on health care?

Koch: A diverse health care workforce is essential to delivering excellent patient care to a diverse population. Working to mitigate bias in the training of physicians is an important step toward promoting a diverse physician workforce.

ULN: How might this bias be reduced?

Koch: This requires more study. Some ways we might accomplish this include implicit bias training and raising awareness amongst faculty evaluators and revamping assessment tools which may inadvertently promote bias.

ULN: What inspired you to dig deeper into this issue?

Koch: I drew on my own experiences as a woman in medicine, as well as my desire to provide an excellent training experience for the physicians in my internal medicine residency training program.

I have a very specific memory as a resident when I was attempting a difficult procedure and the situation was a critical one. My attending barked at me to allow the male resident to step in to do the procedure instead. I said, ‘No, I’ve got this!’ – and I did. I successfully completed the procedure. 

This is an example of how bias can affect patient care. In the middle of a critical situation where I was trying to fully focus on the patient, I had to remove my focus from the patient and make a split-second decision about whether to stand up for myself. Most examples are, thankfully, not this dramatic. But every experience a trainee has helps to shape them into their future self as a physician.

ULN: Regarding the new funding, what do you hope to learn about gender and ethnicity or race in assessments of residents?

Koch: We hope to quantitate the degree to which race-based bias is present in assessment of these learners and examine whether it exists in synergy with gender bias for those trainees who are both women and underrepresented in medicine. Quantifying its extent is a first step toward better defining the potential problem and then working toward its mitigation.

ULN: What have you learned from this research that you have applied at UofL to increase equity for female residents?

Koch: We have created a Women In Medicine Networking group (WIMN) in the UofL internal medicine residency program. The group holds educational sessions and discussions about issues experienced by women in the field of medicine and as COVID allows, holds social events to encourage networking and mentorship amongst women residents and faculty.

Pancreatic cancer is one of the most deadly cancers. The five-year survival rate is just 10% for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. Further, one promising area of cancer treatment, immunotherapy, has not provided benefit for pancreatic cancer patients.

University of Louisville researchers recently have shown that beta-glucan, a natural carbohydrate, can generate enhanced immune responses to cancer in the pancreas and may lead to improved efficacy of immunotherapy for pancreatic cancer.

Jun Yan, chief of the Division of Immunotherapy in the Department of Surgery at UofL, said one of challenges for pancreatic cancer is that natural immune cells are unable to enter the pancreas to combat the growth of tumors, creating an immune desert.

“These tumors lack quality effector immune cells that can kill them,” Yan said. “In addition, pancreatic cancer has a unique tumor microenvironment that prevents the influx of anti-tumor immune cells.”

In new research published this month in Nature Communications, Anne Geller, an MD/PhD student, and a research team at UofL led by Yan demonstrate that a type of beta-glucan derived from yeast can alter the environment within the pancreas to promote anti-cancer immune cell migration to the site of the cancer. Beta-glucan, a naturally occurring carbohydrate found in plants, bacteria and fungi, is known to induce trained immunity, stimulating an immune response to a specific stimulus, such as pancreatic tumor cells.

Trained immunity is a new concept in the field of immunology and is the idea that innate immune cells possess a form of “memory,” which typically only has been considered to be a feature of adaptive immune cells such as T-cells. Using animal models, Yan and his team found that when they injected particulate beta-glucan into the peritoneal area, it accumulated in the pancreas and promoted anti-cancer immune cell migration to the area. These immune cells were found to have a trained immunity phenotype and effectively inhibited pancreatic cancer growth.

“This research demonstrates that a natural compound can stimulate trained immunity in pancreas,” Yan said.

The researchers also found that beta-glucan-stimulated trained immunity can enhance PD-1 antibody therapy in pancreatic cancer. Anti-PD-1 immunotherapy has been approved to treat many types of cancer including melanoma and lung cancer. However, this therapy has failed in treating pancreatic cancer. This research could be a breakthrough in successfully applying immunotherapy to pancreatic cancer.

“This research has a great potential for clinical translation as it elucidates a strategy for delivering therapeutics directly to the pancreas, identifies a mechanism of enhancing anti-tumor immune responses against pancreatic tumors and provides insight into ways of unleashing the awesome power of immunotherapies against PDAC,” Geller said. “This could be a breakthrough in treating the deadly cancer that has evaded so many other forms of treatment.”

Yan, director of the Immuno-Oncology Program at UofL Health - Brown Cancer Center and study coauthor, and surgical oncologist Robert C.G. Martin II are conducting a clinical trial using beta-glucan in pancreatc cancer patients as a proof-of-concept study.

“This publication demonstrates that a simple yeast-derived beta-glucan supplement has the potential to enhance a patient’s immune system and then respond more effectively to therapies in pancreatic cancer. The concept that patients’ immune systems can be ‘trained’ to see their pancreatic cancer as abnormal or foreign could be a crucial step in enhancing a patients’ overall survival and thus quality of life,” said Martin, professor and director of the UofL Division of Surgical Oncology and a co-author on the study.

According to the American Cancer Society, more than 60,000 adults are expected to be diagnosed with pancreatic cancer in the U.S. in 2022 and nearly 50,000 patients will die from the disease. Alex Trebek, long-time host of the game show “Jeopardy!” shared his pancreatic cancer diagnosis and treatment journey beginning in 2019. Trebek died in 2020, just over 18 months after announcing his diagnosis.

“UofL is committed to solving big, global challenges through research,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “This work, leveraging the power of the immune system to better treat pancreatic cancer, could have a big impact in helping people live lives that are not just longer, but healthier and more resilient.”

Funders: NIH/NCI R01CA213990 and the Endowment in translational research

DOI:  10.1038/s41467-022-28407-4

http://www.nature.com/ncomms

http://www.nature.com/articles/s41467-022-28407-4

Becoming a doctor is more than learning anatomy and medicine for a group of University of Louisville medical students. They want to help children affected by violence in Louisville.

Whether they are victims themselves or witness violence involving someone they know, children exposed to violence experience emotional and psychological trauma. A group of social-justice-minded students in the UofL School of Medicine have created Future Healers, a mentorship program to provide these children with new goals and new role models.

The idea grew out of the White Coats for Black Lives rally held on the Health Sciences Center campus in June 2020 in support of health equity and social justice. Members of the UofL chapter of the Student National Medical Association (SNMA) who spearheaded the rally wanted to continue work to mitigate the effects of violence in the city, which has been rising over the past several years.

“The rally was great, but that was just a temporary way for us to show support,” said Karen Udoh, a third-year medical student and then-president of the UofL SNMA chapter. “We were brainstorming about how we could get our departments and students involved with long-term initiatives that really would be an asset for the community.”

With support from SNMA faculty advisers Keith Miller and Christopher Jones in the UofL Department of Surgery, along with the UofL Health - Trauma Institute and Christopher 2X, a local anti-violence advocate and executive director of Christopher 2X Game Changers, they formulated the program to help children overcome the effects of violence by inspiring them to become healers themselves.

The Future Healers program was born.

Following a pilot program with preschoolers at the Chestnut St. YMCA in early 2021, the students worked with Miller, a trauma surgeon, and Jones, a transplant surgeon, to create a series of videos and interactive learning modules for preschoolers to young teens that teach them about anatomy, health and healing and introduce the idea of becoming a health care professional.

The students present the modules at monthly sessions for the preschoolers and for Future Healers Ambassadors, kids from the community ranging in age from 4 to 13 who have been exposed to violence. As of February, the Ambassadors included 80 kids, with 10 more preschoolers participating through the YMCA.

“These students and the surgeons are providing hopeful images to show these kids a different path, to get them interested in the medical arena,” 2X said.

UofL alumna and SNMA member Zahara Gully, director of the Future Healers education committee, said they try to put themselves in the place of the kids as they develop the programs.

“We thought about ways our younger selves would have enjoyed learning about medicine and health. We incorporated a lot of hands-on activities,” Gully said. “The first activity we did, in October, was around nutrition and the food groups. We had the kids decorate fruit as Halloween characters. We had pompoms and bandage tape and they dressed up bananas as mummies.”

Gully, who teaches anatomy and biology at Jefferson Community and Technical College, said she hopes the kids retain at least some of the information.

“Of course, not everything is going to be remembered, but to have kids say, ‘Mom, I know what the strongest bone in the body is! It’s the femur!’ Those moments are priceless,” she said.

In addition to getting the kids interested in the sciences, medicine and health care, the monthly sessions include a care component to help them cope with stresses related to exposure to violence.

“We have additional elements to make sure we're taking care of their other needs as well, because a lot of them are coming into our space just having a loved one shot earlier that week or hearing gunfire the night before,” Udoh said. “They're constantly being exposed to violence, so we always take time within our sessions to address mental health to have different exercises where there are ways for them to express themselves.”

For May, the group is planning an entire session focused on mental health with assistance from child psychiatrists and psychologists.

2X believes the Future Healers program will help give the kids an alternative vision for their lives.

“It’s not their job to stop the violence, but these medical students and the doctors are creating a narrative that they are here as healers and want to be an example to these young victims,” 2X said. “There is no better partner than UofL and UofL Health, with the medical students and the surgeons showing an interest in these kids. You can’t describe the value of that. The kids and the parents have bought into it. It’s unique, it’s magical.”

The medical students also volunteer for other Ambassadors events, such as the Got Zoo Buddies program at the Louisville Zoo. They students are motivated to help the kids, but as future physicians, the understanding they gain about their community also is valuable.

“Our mission with Future Healers is to build better bridges between health providers and the communities they serve,” said Satya Alluri, a third-year UofL medical student and Future Healers wellness director. “Not only is it beneficial for the kids to have representation, to see people of color as doctors and have mentors to help them dream bigger, it helps us as future physicians to see first-hand how our current socioeconomic structures impact the health and well-being of patients. It helps us become better physicians and surgeons.”

Briana Coleman, a third-year UofL medical student and Future Healers technology director, appreciates the opportunity to make a difference for her community even while she is preparing for her career in medicine.

“It's a passion of mine to help out with the community,” Coleman said. “You don't want to see any violence or any bad things happen to the people around you. My message to all is you need to get out there get involved in anything because you can really make a difference, even if you are just a student.”

To learn more or to get involved, email Future Healers.

Imagine reliving your entire life in the space of seconds. Like a flash of lightning, you are outside of your body, watching memorable moments you lived through. This process, known as “life recall,” can be similar to what it is like to have a near-death experience.

What happens inside your brain during these experiences and after death are questions that have puzzled neuroscientists for centuries. 

However, a new study  from Dr. Ajmal Zemmar of the University of Louisville and colleagues throughout the world, “Enhanced Interplay of Neuronal Coherence and Coupling in the Dying Human Brain,” published in Frontiers in Aging Neuroscience, suggests that your brain may remain active and coordinated during and even after the transition to death, and be programmed to orchestrate the whole ordeal.

When an 87-year-old patient developed epilepsy, Dr. Raul Vicente of the University of Tartu, Estonia, and colleagues used continuous electroencephalography to detect the seizures and treat the patient. During these recordings, the patient had a heart attack and passed away.

This unexpected event allowed the scientists to record the activity of a dying human brain for the first time ever. 

What did they find?

"We measured 900 seconds of brain activity around the time of death and set a specific focus to investigate what happened in the 30 seconds before and after the heart stopped beating,” said Zemmar, a neurosurgeon at the University of Louisville, who organized the study.

“Just before and after the heart stopped working, we saw changes in a specific band of neural oscillations, so-called gamma oscillations, but also in others such as delta, theta, alpha and beta oscillations.” 

Brain oscillations are more commonly known as brain waves. They are patterns of rhythmic brain activity normally present in living human brains. The different types of oscillations, including gamma, are involved in high-cognitive functions, such as concentrating, dreaming, meditation, memory retrieval, information processing and conscious perception, just like those associated with memory flashbacks.

“Through generating brain oscillations involved in memory retrieval, the brain may be playing a last recall of important life events just before we die, similar to the ones reported in near-death experiences,” Zemmar speculated.

The findings question what we believe we know about the moment of death.

“These findings challenge our understanding of when exactly life ends and generate important subsequent questions, such as those related to the timing of organ donation,” Zemmar said.

“Every human alive has at some point an encounter when they lose a loved one and every one of us someday will go death themselves, so the interest obviously has been there. I've lost my grandfather. I've lost my grandmother with whom I was very, very close,” Zemmar said.

“And you ask yourself, what does the brain do? As a Ph.D. in neuroscience and a neurosurgeon, you think about these things.”

What do the findings tell us?

“You could probably categorize it in in three different categories to say what can we take from this,” Zemmar said. “One is scientific, one is metaphysical and philosophical and one is spiritual.

“Scientifically, it's very difficult to interpret the data because the brain had suffered bleeding, seizures, swelling – and then it's just one case. So we can't make very big assumptions and claims based on this case.

“On the metaphysical side, if you have these things, it is intriguing to speculate to say that these mechanisms – these brain activity patterns that occur when we have memory recall and dreaming and meditative states – they recall just before we go to die. So maybe they're letting us have a replay of life in the last seconds when we die.

“On the spiritual side, I think it is somewhat calming. I face this at times when you have patients that pass away and you talk their families; you have to be the bearer of bad news. Right now, we don't know anything about what happens to their loved one’s brain when they're dying. I think if we know that there is something happening in their brain, that they are remembering nice moments, we can tell these families and it builds a feeling of warmth that in that moment when they are falling, this can help a little bit to catch them.

“It opens an interesting question to me on when you define death. That plays a big role for questions such as, when do you go ahead with organ donation? When are we dead? When the heart stops beating because the brain keeps going. Should we record EEG activity in addition to EKG to declare death? This is a very, very interesting question for me. When is exactly the time when we die? We may have tapped the door open now to start a discussion about that exact time onset.”

Researchers at the University of Louisville analyzed data for heart transplants from 1987 to 2019 to better understand equity in access to heart transplant for adult Black and white patients and those of other races, comparing percentages of patients who were placed on the transplant list and those actually transplanted over time. They found that access to transplants for Black patients has improved significantly over the study period, both in the percentage of patients listed for transplant and the percentage of transplants performed.

Jaimin Trivedi, assistant professor and director of clinical research and bioinformatics in the UofL Department of Cardiovascular and Thoracic Surgery, was lead author on an article published in PLOS ONE last month detailing the findings.

Trivedi and his colleagues in the department used data from the United Network for Organ Sharing (UNOS) database to analyze changes in the percentage of heart transplants for Black, white and patients of another race since 1987, when the database was established. They analyzed de-identified records for a total of 105,266 adults listed in the database for heart transplants from 1987 through 2020 by Black, white or another race, and the 67,824 patients from the list who received a heart transplant.

The proportion of Black patients on the UNOS heart transplant list increased form 7% in 1987 to 25% in 2019 and those who received transplants increased from 5% in 1987 to 26% in 2019.

According to 2020 U.S. Census data, 14.2% of the U.S. population is Black or African American alone or in combination with another race.

“Black patients historically have had poorer access to heart transplants, evident in our study as fewer patients listed for transplant and fewer patients actually receiving the transplant,” Trivedi said. “But, as the general health care of heart transplant patients improved over the years and the knowledge of racial disparities came into light, all these things came together and eventually the proportion of Black patients listed increased over time.”

While the numbers indicate parity among patients of different races, Trivedi said an analysis of equity must also consider the increased risk for heart disease among Black patients.

“The Black population is at higher risk of cardiac disease based on the CDC data, so that means there are more Black patients likely to have heart failure and they are more likely to require a heart transplant,” Trivedi said. “If we are just looking at two numbers in the proportion of patients transplanted right now, it's improved, but we have to look at it from the perspective of how prevalent heart disease is in the Black community and then how many of them are getting a transplant. So more research has to be done before you can meaningfully say whether there is equity in access to heart transplants.”

The researchers examined three-year survival of heart transplant patients. Post-transplant outcomes improved for all patients over the study period due to better post-transplant care, more rapid treatment of transplant rejection and other factors. Outcomes also improved for Black patients, which are reaching levels comparable to white and other patients in recent years.

“There has been a general improvement in transplant survival outcomes across the races. Black patients tended to do slightly more poorly than white patients, but when we look at more recent data over the past five or six years, we have seen that Black patient survival also has been improving and it is reaching par.”

Another factor affecting post-transplant survival is access to quality health insurance. With this in mind, the researchers compared data for individuals with private insurance with those who had Medicare or Medicaid, information that was included in the database since 1994.

They found that post-transplant survival for Medicare and Medicaid patients improved over time but remained marginally below that of private insurance patients. The improvement in survival of Black patients was seen through all insurance classes over time, particularly since 2012, which Trivedi said could be multifactorial but also partially due to reliable insurance coverage after the application of the Affordable Care Act.

Toni M. Ganzel, MD, MBA, dean of the UofL School of Medicine, joined UofL in 1983 as an assistant professor of otolaryngology. In 2001 she was named associate dean for student affairs and in 2003, senior associate dean for students and academic affairs. In 2013, Ganzel became the first female to be appointed dean of the UofL School of Medicine. In 2020, she was appointed vice president for academic medical affairs.

In honor of International Day of Women and Girls in Science, UofL News talked with Ganzel about her journey into medicine and science.

UofL News: Tell us about your journey into medicine.

Toni Ganzel: I didn’t grow up with the goal of going into medicine. In fact, my first life aspiration that I can remember was wanting to be Wonder Woman because I fancied the idea of flying around the world and saving people. And I also was fond of the red high heel boots and the outfit.

The sixth grade was a pivotal time in deciding what career to pursue because it was then that I fell in love with science. Science mesmerized me – especially biology – and I was fascinated by how the body worked. So, what I thought I wanted to do then was to be a high school biology teacher. My other two areas of avid interest in middle school and high school were cheerleading and student government. This led to deciding my dream job was to be a high school biology teacher, cheerleading coach and student government sponsor.

But when I got to college and took more advanced sciences, I realized that teaching high school biology may not challenge me enough and I considered medical research instead. A friend suggested I take the MCAT and go into medicine, which is something I hadn’t considered. I took the advice, took the MCAT, applied to medical school, got accepted and have never looked back. I can’t imagine any other profession bringing me the joy and fulfillment that being a pediatric ENT surgeon and medical educator did. And for the past 10 years, being the dean is equally rewarding and has been an amazing opportunity to help shape the future of the institution and to work every day with talented students, residents, faculty and staff.

My path to medicine was almost serendipitous and I tell students today that path doesn’t necessarily work for everyone, that more intentionality is needed. As I take a step back and think about how to find the sweet spot of a career, it’s marrying your goals and passions and seeking opportunities to bring those two things together. I loved science, loved helping people and loved learning. Medicine was the perfect marriage.

UofL News: What are some of the biggest challenges you have faced in your career?

Ganzel: The biggest challenge was and is the time commitment. The time challenge started in medical school and has continued ever since. While I try and make a conscious effort to balance work and family, it’s always a struggle.

UofL News: What has been your most rewarding moment in medicine?

Ganzel: Rather than a single moment, it has been a series of moments and it’s on really two tiers – thinking about being a physician versus thinking about being dean. My field of training was ENT surgery and specifically pediatric ENT, so I did lots of tonsils and tubes and airway work and every one of those was so rewarding. I probably did 15,000 tubes and 10,000 tonsillectomies and adenoidectomies, and never got bored. Children had repeated ear infections and hearing loss and they nearly always got better when they got tubes. Children snored and obstructed at night from large tonsils and adenoids, and they nearly always got better when they had their tonsils and adenoids out. It was so gratifying to be able to improve the quality of life of not just the children, but their families as well.

Then, when I think about being the dean, and previously the student affairs dean, it has been so rewarding to touch students’ lives and watch their own professional growth and development. I had the joy of teaching students and then watching them develop incredibly successful careers as physicians and as leaders. Now, as dean, I not only get to work with students and trainees, but with incredible faculty and staff and fantastic colleagues and leaders across the institution and across the country. I am very blessed to be able to do work that I love.

UofL News: What would you tell other women interested in joining the medical field?

Ganzel: If you love science, if you love learning, if you love helping people, it is a wonderful field. However, you also need to be mindful of the time commitment because it’s a big one. And while work-life balance will be a challenge, it is a profession that will bring you great joy, humility and gratification.

UofL News: What is one thing you wish you could tell your past self during medical school?

Ganzel: I would tell myself to remember that medical school is not a destination, but it’s part of a career journey. And on those days that feel daunting, to keep the long view in mind and take time to remember why I chose this life career.

UofL News: What do you like to do outside of work?

Ganzel: I love spending time with my family and my dogs. I like to exercise, my husband and I like to travel and we love mountain sports of hiking, skiing and mountain biking. And while we like to be active, we also enjoy reading and relaxing as well. 

UofL News: What is your hope for the future of medicine?

Ganzel: That this pandemic gets over. It has been a nightmare. But I’m proud of the way that we have risen to the occasion and the resilience that we have shown.

Another hope for the future of medicine is that our increased focus and commitment around health equity will result in better health care and better health for all. Finally, I hope that our research discoveries will continue to lead to new cures and healthier people.

Nearly four decades after Henry Stifel’s spinal cord injury – and after following spinal cord injury research as a philanthropist for more than three – the opportunity came for him to participate in epidural stimulation research at the University of Louisville.

On one level, it was a dream come true, but he had to think carefully about it before accepting.

Before he enrolled, he took stock of his goals. Did he have expectations about what he might gain? Was he doing it only for himself? Finally, he was about to get married and it would require relocating to Louisville from his home in New York City for an extended period of time.

Ultimately, he decided his participation could benefit other older SCI patients and those longer post-injury – he was 55 years old and 39 years post injury. The possibility that he could benefit personally was a bonus – but an exciting one.

“My wife said I would be regretting it for the rest of my life if I didn’t do it,” Stifel said. “I admit I was like a kid in a candy shop – I wanted that candy! But I knew I would have to work extra hard.”

From philanthropist to participant

Stifel was 17 years old in 1982 when an auto accident left him paralyzed, unable to walk or use his hands. With support from his family and community, he got on with life, graduating from high school, then college with a degree in finance and pursuing a career on Wall Street.

Hoping to change the trajectory of spinal cord injury research, dubbed the “graveyard of neuroscience,” Stifel and his father started a foundation to raise money and fund research that would give hope for recovery to people with spinal cord injuries. That foundation eventually merged with the American Paralysis Association and later with what now is known as the Christopher and Dana Reeve Foundation, supporting research and advocacy for individuals with spinal cord injury (SCI).

As a board member of the foundation throughout its history, Stifel followed the work of SCI researchers, particularly UofL professor Susan Harkema and Kentucky Spinal Cord Injury Research Center. He was impressed with the progress they made using implanted epidural stimulators, from Rob Summers, the first individual implanted with a stimulator for SCI research, to additional participants who experienced voluntary movement, improved cardiovascular function, the ability to stand and improved bowel, bladder and sexual function. Some even took steps because of the implant and specialized therapy developed by the UofL team.

Stifel, now in his 50s, was gratified to see this progress and support the work through the foundation, including “The Big Idea,” a 36-participant study of the benefits of epidural stimulation funded by the Reeve Foundation and led by Harkema. The previous participants were younger and had a shorter length of time since their injury. Although he had been to Louisville to participate in other studies, Stifel believed that because it had been nearly 40 years since his injury, it was unlikely he would be able to participate in the epidural stimulation studies.

Then in 2018, Stifel got a call to participate in The Big Idea. Since his deficits were stable, which gave the researchers a solid starting point to document any gains or changes he might experience, he qualified.

When he arrived in Louisville for the study in 2020, he knew that nothing was guaranteed.

“I understood that you need to go in with zero expectations,” Stifel said. “You can only have expectations if the therapy is proven, but it is still being tested. My goal was to be involved and represent others who are injured as long as me. I wanted to help the research progress.”

Blood pressure regulation and stand training

Stifel’s overall health had remained relatively stable in the years since his injury, without many of the comorbidities people with severe SCI often experience. The one side effect he did have was chronic low blood pressure.

“My blood pressure was typically 80/50, which can be debilitating,” he said. “I became used to it, but it is not a healthy way to live. When I was giving a presentation or having a conversation, I would find myself distracted.”

Once enrolled in the study, Stifel underwent preliminary assessments followed by the surgery to implant the electrode on his spine and the epidural stimulator in his abdomen. Then the researchers did a series of mapping sessions in which the stimulator was tested for each of the areas being studied: voluntary leg movement, trunk control and cardiovascular function.

Stifel was randomized into a cardiovascular arm of the study, which required that he monitor his blood pressure every 15 minutes for six hours a day, keeping his systolic blood pressure between 110 and 120. If it dropped below that, he was to adjust the stimulator to regain that level.

Those sessions brought significant improvement for Stifel.

“I didn’t realize how poorly I felt until it was fixed. I guess you have to feel bad to realize what good feels like,” he said. “When my blood pressure maintains a healthy level, it is like a breath of fresh air. My ability to engage, be proactive and live life is so much easier.”

Now, even when he turns off the stimulator, his blood pressure remains above its previous levels for several hours.

Stifel’s study protocol also included 160 two-hour stand training sessions in the lab at UofL Health – Frazier Rehab Institute. Every weekday, he would stand upright in a standing frame with trainers supporting his back, chest and each knee. These sessions were to help Stifel gain strength and independence.

“At the end of the sessions, I could consistently stand for 10-to-16 minutes without knee support,” Stifel said. “The epidural stimulator is more intense and effective than anything else I have experienced.”

Moving the needle

Stifel’s time since injury is the longest of any of the participants in the UofL studies so far.

“I am more of an outlier on the low end, but at 56 years old and nearly 40 years post injury, I think I did great,” he said.

Even Harkema was somewhat surprised that Stifel regained voluntary movement as soon as his early sessions led by Claudia Angeli, assistant professor of bioengineering and director of the epidural stimulation program at KSCIRC.

“I admit we had low expectations of Henry being able to move voluntarily after almost four decades of no movement,” said Harkema, professor of neurological surgery and associate director for KSCIRC. “Even though it supported our theory of the sophistication of the human spinal circuitry, I was stunned when Dr. Angeli was able to find stimulation configurations for him to sit independently and move his toes, ankles, knees and hips in the first sessions. Importantly, this shows that under the right conditions, recovery can happen even decades after injury.”

Now that he has completed his initial part of the study, Stifel is taking part in another study arm in which he will complete another 80 sessions focusing on trunk control and voluntary leg movement.

Once he completes the additional studies, Stifel plans to incorporate training with the stimulator in his daily exercise routine. Although he is not steady enough to stand on his own at home, he will continue that training along with blood pressure regulating, core exercising and any other positive outcomes that might come from this new phase of the study.

“I don’t want to do this study and then shelve it. We accomplished a lot and I want to be able to do more.” Stifel said. “I feel like I won the senior golf tournament, but I still want to beat the kids that have won the Masters. It’s human nature to want more.”

He also is happy to have contributed personally to the overall body of research.

“I think I have helped them move the research needle,” Stifel said. “There have been so many exciting discoveries. Spinal cord injury research has moved from the graveyard of neurological research to interventions that are impacting lives today. This field of research is quickly moving from the traditional fundraising path to one of venture philanthropy and gaining the interest of true capital. Lives are being changed thanks to epidural stimulation, transcutaneous stimulation and the other work being done here and elsewhere.

“This is an amazing research study within the walls of an amazing university. I hope the Louisville community is aware of it and proud of the accomplishments coming from it. It is an amazing time for this field of research.”

Visit Henry Stifel’s blog about his journey with epidural stimulation research at http://henrysjourney.com.

To support spinal cord injury research at the University of Louisville, visit VictoryOverParalysis.org.

When she was growing up, Shannon Strader experienced constant pain and nausea. When she was a senior in high school, she was diagnosed with a rare kidney and vascular disease, Posterior Nutcracker Syndrome, in which the vein from her left kidney is anatomically displaced and compressed between her spine and aorta.

During the summer between high school and college, Strader underwent the first of three surgeries to treat her condition. As a college sophomore, struggling to sustain her college education and social life while navigating her health issues, she looked for ways to connect and share support with other students with similar experiences.

“There was no national organization to support people with all types of disabilities – only specific types of illnesses,” Strader said. Because it is extremely rare, no support group exists specifically for her illness.

So Strader, now a second-year medical resident at UofL, created a blog to share her experience and to connect with other college students with long-term health problems. She went on to establish Bella Soul, a non-profit organization to provide scholarships and emotional support to students facing chronic illness or disability. Strader assembled a board of directors that included college classmates and other advisers, established the 501(c)3 corporation with support from family, friends and her school – the University of Wisconsin – Madison, and began accepting donations.

Bella Soul awarded the first three scholarships in 2013.

“Since then, we have awarded 50 scholarships to young adult students to help with medical bills or other expenses related to their illness or disability,” Strader said. Strader said Bella Soul receives 50-100 scholarship applicants for every scholarship available and has given between 2 and 10 scholarships each year, depending on funds raised that year.

Reviewing all the applicants is time consuming, Strader said, but she is glad to be able to connect with each of the students, who apply by sharing their stories and proof they are students.

“It is exhausting, but all very amazing,” she said.

As an undergraduate, Strader studied neurobiology and stem cell sciences and worked in the regenerative biology lab of James Thomson at the Morgridge Institute for Research at UW – Madison. Her interest in stem cells is motivated by her own illness as well as that of her twin sister, Lauryn, who had cerebral palsy and died when they were 8 years old.

After graduating from UW – Madison, Strader obtained a master’s in biomedical sciences and received her medical degree from Lincoln Memorial University – DeBusk College of Osteopathic Medicine in Knoxville. She chose UofL for her residency training in physical medicine and rehabilitation because of the extensive inpatient opportunities available to the residents at UofL Health – Frazier Rehab Institute. She hopes to pursue clinical care as well as conduct biomedical research into neurological disabilities such as cerebral palsy.

“I came to UofL because the program was one of only a couple of places that offer good inpatient experience caring for individuals with complex disabilities,” she said. “My main goal is to figure out better treatment options for these individuals. Their treatment options have not changed in 20 years.”

For nearly three decades, John Pierce Wise Sr. has investigated the connection between exposure to metals and cancer, working both in the lab and in the field, reporting significant discoveries about the effects of metals on chromosomes in lung cancer and how those effects differ in humans and in whales.

Wise, professor in the University of Louisville’s Department of Pharmacology and Toxicology, now has received $6.7 million over eight years from the National Institute of Environmental Health Sciences through the Revolutionizing Innovative, Visionary Environmental health Research (RIVER) program to investigate how chromosome instability resulting from exposure to metals leads to lung cancer.

Lung cancer is the leading cause of cancer death in the U.S., and Kentucky has the highest rates of lung cancer incidence and mortality of any state. Despite the widely held perception that lung cancer is simply attributed to smoking, 1 in 5 women and 1 in 12 men who develop lung cancer never smoked. In addition to high rates of cancer, lung cancer has a five-year survival rate of 21%, one of the lowest of any cancer site.

“Lung cancer has a substantial impact on human health, particularly here in Kentucky, and it is time the misconception that smoking is the only cause of lung cancer is dispelled,” said UofL interim president Lori Stewart Gonzalez. “We are grateful for the institute’s confidence in Dr. Wise and our university to lead this work in addressing such a significant health concern. I am excited to see this amazing research continue and expand at UofL thanks to this grant.”

Metals are some of the top environmental causes of human lung cancer, but scientists do not fully understand how the metals cause cancer. Wise’s research has shown that one such metal, hexavalent chromium, causes chromosome instability, in which the chromosomes are increased, deleted or rearranged in inappropriate ways. This chromosome instability can lead to the development of cancer.

Wise has studied metals-induced chromosome instability in humans and animals. Through his field work in sampling skin and blubber from whales, Wise has discovered that while the animals are exposed to hexavalent chromium in the ocean, it results in much less chromosome instability and cancer.

“What’s thought to underlie that is a double-strand break in the DNA helix. In human and whale cells, chromium induces the same number of breaks, so you would expect the same amount of effect on the chromosomes, but you don’t see that,” Wise said. “One of the things we’ve found is that chromium also inhibits the repair of these breaks in humans – you get the breaks and you can’t fix them. In whale cells you get the breaks, but you can fix them. What about whales is protective or corrective? That’s what we’re digging into.”

Wise has assembled a team of researchers from around the world to investigate this process further with the hope that this knowledge ultimately will lead to ways of preventing and reversing metals-induced lung cancer in people.

The research will include laboratory studies and then translate those findings to wildlife and human populations of workers exposed to metals. In addition to Wise, project researchers include KeJian Liu of the University of New Mexico, who will lead lab studies and Tongzhang Zeng of Brown University, who will lead work with human populations. Doctoral students in Wise’s lab and UofL faculty members Sandra Wise, Michael Merchant and Matt Cave also will participate, along with additional researchers in the U.S., Germany, China and Japan.

“UofL is one of the top institutions in the country in research and discovery for how human health is influenced by our environment, and preeminent researchers like Dr. Wise are the reason,” said Kevin Gardner, UofL executive vice president of research and innovation. “This grant is recognition of the incredible contributions Dr. Wise has made to the field and provides ongoing support for continued discovery for years to come.”

RIVER grants are awarded to select investigators who have shown a broad vision and potential for impactful research. They allow the investigator increased flexibility and the freedom to set specific research goals toward a given objective, adjusting the research based on new findings, without seeking new funding. Cave received a RIVER grant in 2017 to conduct research into the effects of environmental exposures on fatty liver disease.

An interdisciplinary team of researchers from several institutions headed by the University of Chicago and including the University of Louisville has found evidence that cannabidiol (CBD), a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in mice.

The study, published Jan. 20 in Science Advances, found CBD showed a significant negative association with SARS-CoV-2 positive tests in a national sample of medical records of patients taking the FDA-approved drug for treating epilepsy. The researchers now say that clinical trials should be done to determine whether CBD could eventually be used as a preventative or early treatment for COVID-19.

They caution, however, that the COVID-blocking effects of CBD come only from a high purity, specially formulated dose taken in specific situations. The study’s findings do not suggest that consuming commercially available products with CBD additives that vary in potency and quality can prevent COVID-19.

Scientists have been looking for new therapies for people infected by the coronavirus and emerging variants, especially those who lack access to vaccines, as the pandemic continues across the country and world and as breakthrough infections become more common.

“The Commonwealth of Kentucky has a robust hemp agriculture, so we were pleased to find that pharmaceutical grade CBD is worth testing in future human clinical studies,” said Kenneth Palmer, study coauthor who headed the UofL research team. “In response to the COVID-19 pandemic, our team developed expertise in SARS-CoV-2 infection models and we welcomed the opportunity to collaborate with the University of Chicago team to confirm the efficacy of CBD treatment against SARS-CoV-2.” 

Palmer is director of the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases and the Leona M. and Harry B. Helmsley Charitable Trust Endowed Chair in Plant-based Pharmaceutical Research at UofL. The center houses the Regional Biocontainment Laboratory, one of only 12 regional and two national biocontainment labs in the United States and the only one in Kentucky. Established with support from the NIH to conduct research with infectious agents, the lab includes Biosafety Level 3 facilities built to the most exacting federal safety and security standards.

Researchers from the University of Louisville co-authoring the study with Palmer are Divayasha Saxena, Jon D. Gabbard, Jennifer K. Demarco, William E. Severson and Charles D. Anderson. The research was directed by the University of Chicago and other scientists involved are from the National Argonne Laboratory, the University of Illinois at Chicago and the National COVID Cohort Collaborative Consortium.

CBD: An unexpected avenue for fighting COVID-19

The idea to test CBD as a potential COVID-19 therapeutic was serendipitous. “CBD has anti-inflammatory effects, so we thought that maybe it would stop the second phase of COVID infection involving the immune system, the so-called ‘cytokine storm.’ Surprisingly, it directly inhibited viral replication in lung cells,” said Marsha Rosner, PhD, Charles B. Huggins Professor in the University of Chicago’s Ben May Department of Cancer Research and a senior author of the study.

To see this effect, UofL researchers first treated human lung cells with a non-toxic dose of CBD for two hours before exposing the cells to SARS-CoV-2 and monitoring them for the virus and the viral spike protein. They found that, above a certain threshold concentration, CBD inhibited the virus’ ability to replicate. Further investigation found that CBD had the same effect in two other types of cells and for three variants of SARS-CoV-2 in addition to the original strain.

CBD did not affect the ability of SARS-CoV-2 to enter the cell. Instead, CBD was effective at blocking replication early in the infection cycle and six hours after the virus had already infected the cell.

Like all viruses, SARS-CoV-2 affects the host cell by hijacking its gene expression machinery to produce more copies of itself and its viral proteins. This effect can be observed by tracking virus-induced changes in cellular RNAs. High concentrations of CBD almost completely eradicated the expression of viral RNAs. It was a completely unexpected result.

“We just wanted to know if CBD would affect the immune system,” Rosner said. “No one in their right mind would have ever thought that it blocked viral replication, but that’s what it did.”

The researchers showed that the mechanism by which CBD blocks SARS-CoV-2 replication involves CBD activation of one of the host cell stress responses and generation of interferons, an antiviral cell protein.

Real world data: Patients taking CBD test positive for COVID-19 at lower rates

The researchers wanted scientific data to show that CBD prevents viral replication in live animals. The team showed pretreatment with CBD for one week prior to infection with SARS-CoV-2 suppressed infection both in the lung and the nasal passages of mice. “These results provide major support for a clinical trial of CBD in humans,” said Rosner.

And the success of CBD wasn’t limited to the laboratory: An analysis of 1,212 patients from the National COVID Cohort Collaborative revealed that patients taking a medically prescribed oral solution of CBD for the treatment of epilepsy tested positive for COVID-19 at significantly lower rates than a sample of matched patients from similar demographic backgrounds who were not taking CBD.  

The potential for CBD to treat patients recently exposed to or infected by SARS-CoV-2 does not precede the first lines of defense against COVID-19, which are to get vaccinated and follow existing public health guidelines for masking in indoor spaces and social distancing. But the published results offer a potential new therapeutic, something still needed as the pandemic rages on.

“A clinical trial is necessary to determine whether CBD is really effective at preventing or suppressing SARS-CoV-2 infection, but we think this may have potential as a prophylactic treatment,” said Rosner. “Maybe you’re in a hot spot or you think you might have been exposed or you’ve just tested positive — that’s where we think CBD might have an effect.”

Not your dispensary’s CBD

The research team emphasized that the COVID-blocking effects of CBD were confined strictly to high purity, high concentrations of CBD. Closely related cannabinoids such as CBDA, CBDV and THC, the psychoactive element enriched in marijuana plants, did not have the same power. In fact, combining CBD with equal amounts of THC actually reduced the efficacy of CBD.

“Going to your corner bakery and buying some CBD muffins or gummy bears probably won’t do anything,” said Rosner. “The commercially available CBD powder we looked at, which was off the shelf and something you could order online, was sometimes surprisingly of high purity but also of inconsistent quality. It is also hard to get into an oral solution that can be absorbed without the special, FDA-approved formulation,” Rosner said.

Furthermore, CBD use is not without potential risks. It appears to be extremely safe when consumed in food or drink, but methods of use such as vaping can have negative side effects, including potential damage to the heart and lungs. It’s also not well studied in certain populations, such as pregnant people, and so should be used only under the supervision of a physician and with caution. 

While the study’s results are exciting, additional study is needed to determine the precise dosing of CBD that is effective at preventing SARS-CoV-2 infection in humans as well as its safety profile and any potential side effects.

“We are very eager to see some clinical trials on this subject get off the ground,” Rosner said. “Especially as we are seeing that the pandemic is still nowhere near the end — determining whether this generally safe, well-tolerated, and non-psychoactive cannabinoid might have anti-viral effects against COVID-19 is of critical importance.”

Rosner was also pleased that this research project was a case study in the power of scientific collaboration by bringing together a highly interdisciplinary group of researchers. Senior authors listed on the paper came from three different research universities and from departments as diverse as microbiology, molecular engineering, cancer biology and chemistry.

“This was truly a team-science effort, and that’s something that really excites me,” said Rosner. “From clinicians to David Meltzer’s group who did the patient analysis to virologists like Glenn Randall, and it goes on and on. This is the way science should be carried out.”