Donghoon Chung, Ph.D., a virologist at the University of Louisville, is one of three principal investigators with a new center working to advance new drugs for the treatment of equine encephalitis viruses in humans. The project, Center of Excellence for Encephalitic Alphavirus Therapeutics, is funded by a $21 million grant from the National Institutes of Health over five years.

The center, headquartered at the University of Tennessee Health Science Center in Memphis, will develop therapeutic drugs to treat three mosquito-borne alphaviruses that cause serious illness in humans and horses: Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV). Although a vaccine is available for horses, there are no FDA-approved treatments or preventive vaccines for these viruses in humans.

Chung, an associate professor in the Center for Predictive Medicine and Department of Microbiology & Immunology at UofL, said the center’s goal is to refine potent small molecule compounds the researchers previously identified as promising as antiviral drugs for treating the encephalitis viruses, and enable those compounds to move to the next step of research, clinical trials in humans.

“In my previous research I found that these compounds inhibit the viral replication cycle. However, we want to further understand which target molecules are interacting with the compound,” Chung said. He described the mechanism of the compounds the group is investigating as similar to the way the drug nevirapine, a non-nucleoside reverse transcriptase inhibitor, works in treating human immunodeficiency virus (HIV).

“This project is to develop a new antiviral compound to treat these diseases in humans,” Chung said. “However, we do not limit our applications of this drug to only humans, as it may be possible to adapt it for treating horses as well.”

These equine encephalitis viruses infect humans and horses through the bite of an infected mosquito. According to the Centers for Disease Control and Prevention (CDC), symptoms of infection include fever, chills, headache and vomiting. Outbreaks of the Western and Venezuelan viruses are uncommon, and an average of only seven human cases of EEEV have been reported annually in the United States over the past ten years. However, the disease may leave people with permanent neurological symptoms, and approximately 30 percent of people who contract the Eastern equine encephalitis virus will die from the disease.

According to Chung, the potential for the viruses to be used in bioterrorism is perhaps even more worrisome. The CDC recognizes viral encephalitis as a Category B human biothreat, making the development of a treatment important.

Chung’s co-principal investigators in the center are Colleen Jonsson, Ph.D., of the University of Tennessee Health Science Center who directs the center, and Jennifer E. Golden, Ph.D., of the University of Wisconsin-Madison School of Pharmacy.

“The goal of our new Center of Excellence is to further develop novel therapeutic molecules discovered by our team that are highly potent across all three viruses, moving the optimal ones forward into pre-clinical development,” said Jonsson, formerly director of the UofL Center for Predictive Medicine.

Chung will test the compounds for toxicity against human cells in vitro, deciphering their molecular mechanisms and determining their resistance threshold utilizing the facilities and staff at the Regional Biocontainment Laboratory at UofL. He also will test the compounds’ resistance threshold that inevitably develops over time, along with Juw Won Park, Ph.D., assistant professor of computer engineering in the J.B. Speed School of Engineering at UofL.

Once their work is completed, the researchers expect the new drugs would be ready to begin clinical trial testing in humans.

Three years ago, Lana Boes of Charlestown, Ind., was at the end of her rope. She had been fighting colon cancer for nearly two years with multiple surgeries, two different chemotherapies, regular blood transfusions and more. But the cancer had returned and the chemotherapy no longer was working.

“I was down to 100 pounds. I really couldn’t eat. I had to take medicine to help me with my appetite. I just couldn’t do it anymore,” Boes said.

First diagnosed at age 43, Boes’s first surgery went well, but the cancer returned. After her second surgery, Boes started chemotherapy. Genetic testing revealed she had Lynch Syndrome, a genetic mutation that carries a higher-than-normal risk for cancer. When the first chemotherapy drug failed her, Boes started another, harsher chemo drug. That drug, too, eventually failed.

At that point, she was offered the chance to participate in a clinical trial for pembrolizumab, better known as Keytruda®, an immunotherapy drug previously successful in treating other types of cancer, but not yet FDA approved for the type of cancer Boes had.

“Lana started to suffer not only from the side effects of her cancer progressing, but also the side effects of treatment. It was clear that we needed something new and different,” said Rebecca Redman, M.D., Boes’s oncologist and deputy director of clinical research at the UofL James Graham Brown Cancer Center. “This clinical trial became available right around that time. It was based on some early evidence that suggested immunotherapy would be a really great option for Lana’s type of cancer.”

Keytruda is a type of immunotherapy that engages a patient’s own immune system to fight cancer. Cancer cells use a protein called PD-1 to hide from the immune system. Keytruda blocks the PD-1 pathway, Redman said, allowing the patient's immune system to recognize the cancer as something that doesn't belong and destroy it.

With support from her husband, Tim, Boes decided to enter the trial. She started receiving Keytruda in June 2016, and her condition improved almost immediately.

“With Keytruda, I got my life back. With chemo I went home and went to bed and you didn’t see me for the weekend,” Boes said. “With Keytruda, I didn’t go home and go to bed. I started getting an appetite and some strength back. I was able to enjoy doing things outside of my house again with family and friends.”

She remained on the immunotherapy drug for two years, completing the trial in June 2018. Regular checkups show that as of March 2019, Boes’s cancer is not detectable in scans or exams, and her cancer tumor marker numbers have remained within normal range. Redman considers her cancer in remission.

Boes says she has a fresh outlook on life, and can plan for her future.

“I used to refuse to book anything in advance. Everything we did was always last minute because I didn’t know if I was going to get to go,” Boes said. “I didn’t buy things that were for the future. I couldn’t talk about the future.”

Now she has plans to celebrate a special milestone in 2020.

“I never used to care about birthdays, but every birthday is a big deal to me now,” Boes said. “I turn 50 next November and I told my husband, ‘I never thought I was going to see 50, so I want to go to Italy.’ It’s huge for me in so many ways.”

While she is grateful for having the chance to participate in the trial with Keytruda, Boes also is grateful to Redman and to the staff at the Brown Cancer Center.

“Just seeing Dr. Redman made me feel better. She saved my life. She treats me with so much care. She sits down and she listens to me,” Boes said. “Every person at Brown is just so kind and they genuinely care. That makes such a huge difference when you are not feeling good.”

Redman, also associate professor at the UofL School of Medicine, said she has seen good results with immunotherapy in other patients with cancer like Boes’s. Unlike chemotherapy, which requires continued treatment, in some cases immunotherapy may allow a patient’s body to continue to control the cancer for an extended period of time.

“The most exciting thing about immunotherapy is that not only are we seeing remarkable tumor responses, but those responses seem to last a long time,” Redman said. “For some patients, it appears that once you train the immune system to attack the cancer, it may continue to do so for some time, possibly even after the immunotherapy has been stopped.”

Keytruda is the first drug approved by the FDA for the treatment of cancers based on a specific change in the DNA of the tumor, microsatellite instability (MSI), instead of where the cancer is in the body. MSI can be present in colon cancer but also in other organ cancers, and Keytruda is FDA-approved to treat cancers with MSI anywhere in the body.

Redman said that through her participation in the trial, Boes helped make it possible for other patients to have access to Keytruda for their MSI cancer. FDA approval typically means an insurance company will cover the treatment and makes the drug available to all patients.

“By participating in this trial, she has allowed this drug to move toward FDA approval, so immunotherapy now is a standard treatment for patients with microsatellite unstable cancers,” Redman said. “Thanks to patients like Lana who participate in clinical trials and take that extra step a little bit into the unknown, thousands of people will benefit and will have their lives turned around.”

Boes is most grateful to have the chance to live without cancer.

“I’m living my life normally,” Boes said. “I’m not cancer. Nobody treats me as cancer. I’m just me again and that is the best feeling ever.”

Participate in clinical trials

Volunteers always are needed to assist researchers solve health problems. Even if you do not have a health concern, you can be part of clinical trial research at UofL and at research institutions around the nation by registering at UofL.me/researchmatch. This nationwide database allows anyone to take part in important health research. Learn more by registering today.

To learn more about cancer clinical trials, visit the UofL James Graham Brown Cancer Center’s clinical trials page.

A half-million-dollar gift to the laboratory of University of Louisville cardiologist Andrew DeFilippis, M.D., by the late James Ryan will aid in research into biomarkers for cardiovascular disease.

The $500,000 gift to the Division of Cardiovascular Medicine at the UofL School of Medicine establishes the James Ryan Fund for Cardiovascular Biomarker Research. Ryan pledged the gift before he passed away at age 81 in 2018.

“Thanks to Jim, we can help physicians everywhere in diagnosing what is one of the most common causes of death in the world,” DeFilippis said. “He was always interested in others and what their dreams were, their goals in life, their happiness and how he could help.”

The fund will support annual operating expenses for the research led by DeFilippis, who is director of Cardiovascular Disease Prevention and an associate professor in cardiovascular medicine at UofL. DeFilippis is an expert in cardiovascular diseases and cardiac intensive care. His research focuses on cardiovascular risk prediction and the identification of biomarkers that will allow physicians to diagnose the cause of different types of heart attacks, also called myocardial infarction.

A heart attack is death of heart muscle. There are many causes, including the most well-recognized that occurs when one of the heart’s coronary arteries is suddenly blocked or has very slow blood flow secondary to the formation of a blood clot.

Atherosclerotic cardiovascular disease progresses over time, allowing time for screening and early detection. Advances in biomarker research and other developments have led to more sensitive screening methods and a greater emphasis on early detection and diagnosis.

“We’re working to develop biomarkers that will allow clinicians to differentiate among the many different types of heart attacks that can occur,” DeFilippis said. “Not all are the same, and even in the medical community that’s not always given much thought. But if we can differentiate, it will help us better treat patients, allowing us to limit or stop heart damage.”

A biomarker is a biological characteristic that can be measured and evaluated as an indicator of normal biological or pathological processes or a response to a therapeutic intervention. Examples include patterns of gene expression, levels of a particular protein in body fluids or changes in electrical activity in the heart.

Ryan, an active philanthropist and retired insurance executive, suffered from a heart condition himself. A native of Pittsburgh who graduated from UofL and lived most of his life in Louisville, he was on a quest to ensure his estate went to good use. He and DeFilippis forged a friendship through their activities with the American Heart Association. He visited DeFilippis’ lab within the Division of Cardiovascular Medicine several times, even bringing a group of friends.

“He was really involved – he was more than a donor,” DeFilippis said. “He gave advice and offered assistance in business, enabling us to partner with industry to bring our discoveries to market. We really enjoyed his company. The two of us went to lunch several times and talked about lots of things – the lab, his struggles with congestive heart failure and his bucket list. He had a great sense of humor.

“He was an extraordinarily happy man with a deep voice that was very distinctive,” DeFilippis said. “We will certainly miss his presence and his inspiring words about the work we were doing. We take it as a tremendous compliment that he chose to donate to us. Jim was looking for a quality program, great ideas and things that really make sense to improve the health of world.”

DeFilippis and one of his colleagues, Patrick Trainor, Ph.D., recently were invited editorialists for a new study published in the Annals of Internal Medicine that indicates current risk calculators for heart attack and stroke can sometimes be wrong, significantly overestimating some people’s risk while underestimating others' risk. As a result, many people may be unnecessarily taking medication to control risk factors such as high cholesterol and high blood pressure, and others may not be getting enough treatment. The researchers developed a new risk calculation method with a more sophisticated statistical model and newer population data, suggesting it could be more accurate.

To demonstrate the kinds of careers available to women in the science, technology, engineering, mathematics and health (STEM+H) fields, the University of Louisville is hosting its first Girls Rule STEM+H Summit event, Saturday, April 6.

More than 150 girls and young women ages 8-18 are registered to attend the 9 a.m.-2 p.m. event at the Belknap Academic Building. While the 3^rd to 12^th-grade students participate in hands-on workshops and activities, accompanying adults will be offered information sessions on how to prepare for higher education and careers in STEM+H.

Among the workshops, all taught by UofL students and faculty, will be robotics, medicine and genetics.

While UofL has hosted STEM introductory events for girls in past years, 2019 marks the first year health education and careers will be included. The event is co-sponsored by the J.B. Speed School of Engineering, the School of Medicine and the UofL Army ROTC program.

 “We are delighted to once again open our doors and show girls and women the variety of careers in these exciting areas,” said Emmanuel G. Collins, dean of the Speed School. “These careers of the future need more women and under-represented minorities and we hope to inspire by example.”

A short informational video can be found here.

For further information, contact Kari Donahue, 502-852-6279, kari.donahue@louisville.edu.

We’ve all been there. Perhaps you have a mild sore throat and cough on Friday but by Saturday afternoon the cough has worsened. Or you wake up in the middle of the night with extreme nausea and a high fever. What is the most appropriate place to receive care in the most timely manner? 

Primary Care Providers

One of the best ways to care for your own health is to establish a primary care provider (PCP), says Ashley Iles M.D., assistant professor in the University of Louisville Department of Family and Geriatric Medicine and a physician with UofL Physicians Centers for Primary Care at Cardinal Station.

“Primary care refers to medical care given by a provider - physician, nurse practitioner or physician’s assistant. This is the first point of contact for patients’ non-emergent symptoms, disease management and health concerns. 

“For an acute illness like a sinus infection or earache that comes on suddenly during the week, a primary care provider should be your first point of contact,” she said. 

PCPs also encompass preventative types of care including cancer screening, vaccinations, health maintenance exams and patient education. 

“Think of your PCP facility as your medical home,” Iles said. 

Urgent or Immediate Care

An urgent care or immediate care center, however, may be the best option for after hours for worsening acute illness or injuries like mild sprains. These facilities may have an X-ray machine and the ability to perform some lab tests on-the-spot. 

“Think episodic care for urgent care centers,” Iles said. “If you need non-emergency care at a time when you can’t get to your primary care provider, these are good alternatives.” 

But Iles says patients should understand that urgent care facilities don’t keep track of their medical problems, prescriptions or visits the way a primary care provider would. 

“Be sure to follow-up with your primary care provider if you’ve gone to immediate care so they can update your medical records,” Iles. 

Emergency Care

Emergency rooms should be reserved for life-threatening conditions or injuries that could result in serious complications if not immediately addressed, says Adam Ross, M.D., medical director of UofL’s Department of Emergency Medicine.

National statistics indicate that between 5.5 – 8 percent of ER visits are non-urgent.

“However, as you can imagine, someone may come in with chest pain, concerned about a heart attack, and after a workup in the emergency room (EKG, chest x-ray, blood tests, etc.), it’s determined their pain was from GERD or heartburn” Ross said. “While their diagnosis is not an emergent one, the symptom they presented with certainly is.”  

It is better to be safe than sorry, says Ross.

“Always go to the ER when you feel life or limb are at risk: chest pain, shortness of breath, severe headache, weakness, numbness or speech difficulty, severe cuts, excessive bleeding, broken bones or other symptoms with which you are emergently concerned,” he said.

Call 9-1-1 if you are experiencing what seems to be a life-threatening condition. Otherwise, patients can often call their medical insurance company hotlines to speak with an on-call providers that can give advice on what to do. UofL Centers for Primary Care at Cardinal Station can often see patients for acute illnesses or minor injuries the same week. Make an appointment by calling 502-588-8700. An on-call doctor is available to answer urgent medical questions after hours.

About UofL Centers for Primary Care at Cardinal Station

Located at 215 Central Ave. in Louisville, UofL Centers for Primary Care at Cardinal Station offer a full range of primary care services including acute illness visits, annual health maintenance visits, cancer screenings, STI screenings and vaccinations for both children and adults of any age. Additionally, the centers have a wide range of women’s health services including appropriate annual screenings and all types of non-surgical birth control including implantable devices. The office also is home to multiple Sports Medicine specialists who can offer on-site x-rays, acute injury management, chronic conditions management, physical therapy referrals and joint injections. For information and appointments, call 502-588-8700.

The UofL School of Medicine Disaster Medicine Certificate Series will hold an Active Shooter Disaster Drill on the Health Sciences Center campus from 6 a.m. to 3 p.m., Saturday, March 30.

This will be a live-action (not tabletop) drill, complete with actors portraying both perpetrators and victims, and visual, sound and other effects to simulate reality.  The location will be the Instructional Building and the HSC Plaza, 500 S. Preston St. The second floor of Kornhauser Library will be open.

Due to the large-scale nature of this drill, bystanders may hear simulated gunshots or explosions, and see a large police presence on campus. Bystanders should not be alarmed, and should not call 911 as this is only a drill.

In order for this drill to be safe and effective, the number of people on campus must be minimized. If anyone does not have to be on the HSC campus on March 30, please avoid the area.

For additional information, contact Madison Kommor, madison.kommor@louisville.edu, or Jill Scoggins, jill.scoggins@louisville.edu. 

Michael Snyder, a pioneer in the use of big data in biomedical research, will give a free public lecture at the University of Louisville Health Sciences Center on Monday, March 25.

Snyder’s talk, “Big Data and Health,” will take place at noon in room 101-102 at the Kosair Charities Clinical & Translational Research Building, 505 S. Hancock St. Snyder will focus on how information in large databases, or big data, can be used to develop improved and more individualized approaches to predicting, diagnosing and treating common diseases. 

The lecture is sponsored by the Department of Biochemistry and Molecular Genetics at the UofL School of Medicine. For more information, contact Janice Ellwanger at 502-852-5217 or David Samuelson at 502-852-7797.

Snyder, Ph.D., is an international leader in the fields of functional genomics and proteomics and is the director of the Center of Genomics and Personalized Medicine at Stanford University, where he is the Stanford W. Ascherman Professor and Chair of Genetics.

He wrote “Genomics & Personalized Medicine: What Everyone Needs to Know,” a book that explores the prospects and realities of genomics and personalized medicine for consumers. He was a key participant in the Encyclopedia of DNA Elements (ENCODE) project, which identified functional elements in the human genome.

Snyder’s research group was the first to perform a large-scale functional genomics project in any organism. Genomics is a branch of molecular biology that focuses on the structure, function, evolution and mapping of genomes in an organism’s complete set of DNA.

The Snyder Lab has made several groundbreaking findings, including the discovery that much more of the human genome is either transcribed or contains regulatory elements than previously known, and that a high diversity of binding of transcription factors – gene products that participate in regulating what genes are active – occurs between and within species.

Snyder also has combined different advanced “omics” technologies to perform the first longitudinal Integrative Personal Omics Profile (iPOP) of an individual and used the information to assess disease risk and monitor disease states for personalized medicine. He co-founded several biotechnology companies, including Protometrix (now part of Life Technologies), Affomix (now part of Illumina), Excelix, Personalis and Q Bio.

Snyder received his Ph.D. at the California Institute of Technology and postdoctoral training at Stanford University.

Fourth-year medical students now begin the process of planning where they will live and other logistics associated with a move to a new place. Most of the nearly 150 Class of 2019 students recently learned where they’ll complete the next three to seven years of residency training.

Each year, medical students throughout the United States receive their written match notices precisely at noon on the third Friday of March – Match Day. UofL medical students experienced a 97-percent match rate, with 42 percent going into primary care.

The National Resident Matching Program provides a uniform process for matching medical school applicants with residency programs based on the preferences of both. A matching algorithm uses those preferences to match individuals into positions.

Ethan Tomlinson already knew what was in his envelope because of a separate military match program, but he was excited to join his classmates in the Match Day celebration on Friday.

“The true beauty of my medical school experience is the friendships; those relationships and memories are what made the tough times better and the journey worthwhile,” he said.

Tomlinson, who also earned two undergraduate degrees at UofL, will continue his medical training in Internal Medicine as a captain in the U. S. Air Force at Brooke Army Medical Center, Fort Sam Houston in San Antonio.

A native of Louisville, Tomlinson has a family history of military service, including his grandfather who served in the Marines and an uncle who was a fighter pilot in the Air Force.

Although Tomlinson had no military experience prior to medical school, he was accepted into the Health Professions Scholarship Program, where students agree to serve as a military physician in exchange for a full tuition scholarship and monthly stipend. He then joined the Air Force, and went on to complete Commissioned Officer Training and a course in Aerospace Medicine.

Ian Bastian of Madisonville, Ky., also completed medical school through the Health Professions Scholarship Program.

“I have enjoyed my medical school rotations at military treatment facilities,” said Bastian, a second lieutenant in the Army. “Treating soldiers and their families is a rewarding experience, and I look forward to continuing it during residency.”

Bastian will go to Madigan Army Medical Center located on Joint Base Lewis-McChord just south of Tacoma, Wash., for neurology residency training.

“My first encounter with a patient in the neurology clinic at the end of my first year was perhaps the most memorable aspect of medical school,” Bastian said. “Prior to that patient evaluation, I had not considered neurology as a career choice - it was that experience that led me into the neurology specialty.”

Both Tomlinson and Bastian say they are excited about the next step in their educational journeys.

 “I don’t know where my future might take me, but I hope to return to Louisville one day because I love my city. It will always be my first home,” Tomlinson said.

Watch the video from Match Day 2019

A new public health campaign is highlighting the need for education and awareness on antibiotic overuse in Kentucky, the state with the highest rate of antibiotic use in the United States.

Although antibiotics are important life-saving drugs that treat bacterial infections – including strep throat and urinary tract infections – their overuse can lead to drug resistance, which occurs when antibiotics no longer cure infections that they should treat, said Bethany Wattles, Pharm.D., clinical pharmacist in the Department of Pediatrics at the University of Louisville School of Medicine.

Kentucky Antibiotic Awareness (KAA), a statewide campaign to reduce inappropriate antibiotic use, is led by health professional researchers at the UofL Department of Pediatrics Antimicrobial Stewardship Program with collaboration and financial support from the Kentucky Cabinet for Health and Family Services Department of Medicaid Services. The campaign provides education and resources to Kentucky health care providers and the public.

“If we continue to overuse antibiotics, even minor infections will become untreatable. This is a serious public health threat,” Wattles said. “To combat the spread of antibiotic resistance, we must use antibiotics only when necessary.”

Examining antibiotic prescriptions for Kentucky children on Medicaid, researchers found that the rate of antibiotic use has been especially high in Eastern Kentucky. In some areas, children are receiving three-times more antibiotic prescriptions than the national average, Wattles said.

Antibiotics are most frequently used for upper respiratory infections, many of which are caused by viruses that antibiotics do not kill.

The majority of antibiotic prescribing is done in outpatient settings, which include medical offices, urgent care facilities, retail clinics and emergency departments. An estimated 30 to 50 percent of this antibiotic use is considered inappropriate, Wattles said.

When antibiotics are prescribed, it is important to take them as instructed; do not share the medicine with others or save for later use.

To learn more, visit the KAA website and follow the campaign on Facebook and Twitter. Health care providers are also encouraged to join the KAA Listserv for newsletter updates, or email KYAntibx@louisville.edu with questions and suggestions.

Disclaimer: This project was supported by the following: Kentucky Cabinet for Health and Family Services: Department for Medicaid Services under the State University Partnership contract titled “Improving Care Quality for Children Receiving Kentucky Medicaid”, Norton Children’s Hospital, and the University of Louisville School of Medicine, Department of Pediatrics; School of Public Health and Information Sciences. This content is solely the responsibility of the authors and does not necessarily represent the official views of the Cabinet for Health and Family Services, Department for Medicaid Services.

A person’s immune system is affected by a large number of biological, social and environmental influences, many of which change throughout his or her lifetime. This makes it difficult to research certain aspects of immune health by studying living people.

At the next Beer with a Scientist, Fabian Crespo, Ph.D., an associate professor in the Department of Anthropology at the University of Louisville, will explain how bioarchaeologists are studying the skeletons of ancient humans to learn about health and disease.

“By studying different skeletal markers where inflammation is involved, bioarchaeologists can reconstruct immune competence in human skeletal samples. These osteoimmunological findings can help us understand the relationship between immune and bone cells,” Crespo said. “However, to better understand what these findings reveal about human health in the past requires discussion among immunologists, bioarchaeologists and historians.”

Crespo’s talk will begin at 7 p.m. on Wednesday, March 13, at Holsopple Brewing, 8023 Catherine Lane, Louisville, 40222. A 30-minute presentation will be followed by an informal Q&A session.

Admission is free. Purchase of beer or other items is not required but is encouraged.

Organizers encourage Beer with a Scientist patrons to drink responsibly.

UofL cancer researcher Levi Beverly, Ph.D., created the Beer with a Scientist program in 2014 as a way to bring science to the public in an informal setting. At these events, the public is invited to enjoy exactly what the title promises:  beer and science.

Upcoming Beer with a Scientist dates:  April 17, May 15.

March 6, 2019

Antibiotic resistance is one of the greatest infectious disease threats in the 21^st Century. The United States Centers for Disease Control and Prevention (CDC) has estimated that drug-resistant infections are responsible for 23,000 deaths in the United States each year. Among the three most concerning antibiotic-resistant bacteria and fungi identified by the World Health Organization (WHO) is Psuedomonas aeruginosa.

Researchers at the University of Louisville Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM) are working at the forefront in combating these pathogens. The CPM has been testing the effectiveness of new drugs against P. aeruginosa under a contract with the National Institutes of Health since 2013, and a new contract from the U.S. Food and Drug Administration (FDA) will expand the center’s work in testing new drugs against this pathogen. Under the new two-year, $933,606 contract, CPM will develop a validated model for screening antimicrobial drugs against P. aeruginosa.

“This model likely will play an important role in drug development pipelines leading to identification of new antimicrobial drugs,” said Matthew Lawrenz, Ph.D., associate professor of microbiology and immunology who is leading the research. “Researchers at UofL and from around the world will use the model to screen new antimicrobials against multi-drug resistant bacteria prior to clinical trials.”

Forest Arnold, D.O., hospital epidemiologist for UofL Hospital and associate professor in the Division of Infectious Diseases in the UofL School of Medicine, said multi-drug resistant (MDR) bacteria and XDR bacteria, those with resistance to all existing antibiotics, are evolving faster than the drugs to kill them.

“The germs get smarter as we make new drugs. If we are going to stay on top of them, we need new antibiotics, especially new classes of antibiotics -- those with a new mechanism of action that the germ hasn’t seen before,” Arnold said.

Infections with MDR bacteria are particularly threatening for patients with weakened immune systems, those who have had multiple rounds of treatment with antibiotics, and in patients using devices such as ventilators and blood catheters. Since these bacteria are now resistant to many of the antibiotic drugs used to treat them, they can lead to severe infections and death.

“If you have an infection with a bacterium we don’t have an antibiotic to treat, it could kill you,” Arnold said.

P. aeruginosa is common in the environment and in otherwise healthy people, it may cause relatively minor infections of the ear, skin or eye. However, in people with weakened immune systems or in hospital settings, P. aeruginosa can cause serious, life-threatening infections of the blood, lungs, digestive tract or tissue. Infected wounds will have a green pus or discharge and a fruity smell.

The validated animal model, to be developed by UofL researchers with collaborators at the University of Kentucky and the University of Wisconsin, will be used to test new compounds developed by drug companies and research labs around the world against P. aeruginosa. This model will allow testing against multiple strains of pseudomonas and will give more detailed information about the effectiveness of the drugs being tested.

“The previous methods we used for testing the drugs provided basic information about a compound’s effectiveness. This new model will allow us to test anything from older classes of antibiotics to brand new classes and will provide information on dosing and scheduling. In addition, we will be able to test different strategies, such as immunomodulation – targeting the host to better respond to the infection as opposed to directly killing the bacteria,” Lawrenz said.

The CPM’s new contract with the FDA will take advantage of the sophisticated resources at the Regional Biocontainment Lab, located on the UofL ShelbyHurst Campus, which provide the environment necessary for this work.

“This new contract from the Food and Drug Administration supports the development of a model for understanding how bacteria build resistance to current commercially available antibiotics, which in turn, will lead to the discovery of new drugs or methods to combat a variety of infectious diseases,” said Robert Keynton, Ph.D., interim executive vice president for research and innovation at UofL. “The UofL Center for Predictive Medicine and the Regional Biocontainment Laboratory represents a significant investment in infrastructure, faculty and staff by the university in the field of emerging infectious diseases, which is one of our research and training strategic priorities."

March 4, 2019

Recognized as individuals who improve the lives of others, two UofL faculty and two UofL Hospital staff are honored with the Commitment to Compassion Award.

Presented by the Partnership for a Compassionate Louisville, the award is given to health care professionals who inspire others to be more compassionate.

Matt Adamkin, M.D., and assistant professor in the Division Physical Medicine & Rehabilitation, UofL School of Medicine, is among this year’s winners for his work with Special Olympics athletes. Adamkin is a physical medicine and rehab physician in the UofL Department of Neurological Surgery and UofL Physicians – Physical Medicine & Rehabilitation.

His volunteer work with Special Olympics Kentucky includes providing no cost physicals to the special athletes who often suffer from intellectual or developmental difficulties.

Amanda Corzine, M.S.N., R.N., S.A.N.E.-A., and Vicki Yazel, B.S.N., R.N., S.A.N.E.-A., are receiving a joint award for their work at UofL Hospital’s Sexual Assault Forensic Examiner (SAFE) Services, a program that has helped hundreds of sexual assault and domestic violence victims in the Louisville area.

Corzine, coordinator of SAFE Services, was instrumental in implementing an evidence-based domestic violence screening tool in the UofL Hospital Emergency Department that connects victims to immediate advocacy services. She has expanded the office to provide 24-hour availability and new services, including domestic violence forensic exams, the first in Kentucky. Yazel, assistant coordinator of SAFE Services, has strengthened the hospital’s relationships with law enforcement agencies and is improving human trafficking screening in the emergency department.

The fourth UofL recipient is Joseph D’Ambrosio, Ph.D.,Director of Health Innovation and Sustainability at the UofL Trager Institute. He is a licensed marriage and family therapist, and a professor at the UofL School of Medicine. He also teaches couples and family therapy courses for students at the Kent School of Social Work.

D’Ambrosio also is developing a Compassionate Cities Index – a validated measurement of a city’s compassion. The index will be a reliable and accurate tool for measuring the prevalence of compassion in cities.

These honorees will receive an award during the 4th Annual Commitment to Compassion Luncheon at the Muhammad Ali Center on Wednesday, Feb. 27. The event is hosted by Passport Health Plan, Insider Louisville and the Compassionate Louisville Healthcare Constellation. Read more on the Insider Louisville website.

Four UofL faculty were honored as Health Care Heroes this week during an awards presentation by Louisville Business First.

They are:

• Innovator winner - Susan Harkema, Ph.D., professor, Department of Neurological Surgery, UofL School of Medicine; associate scientific director, Kentucky Spinal Cord Injury Research Center; director of research, Frazier Rehab Institute 

Harkema was honored for her research and ongoing commitment to the study of human locomotion. She has dedicated her career to the exploration of technology and development of therapies that will allow individuals with spinal cord injury to recover.

• ·       Innovator finalist - Walter Sobczyk, M.D., pediatric cardiologist, University of Louisville, UofL Physicians – Pediatric Cardiology, Norton Children’s Hospital; associate professor, Department of Pediatrics, Division of Pediatric Cardiology, UofL School of Medicine

A finalist in the innovator category, one of Sobczyk’s career highlights was the pioneering work of his pediatric cardiology group to use computer technology to transmit cardiac ultrasounds remotely from small community hospitals throughout the state of Kentucky. This important advancement helped provide high-level care to underserved areas of the state.

• Provider Winner -Erle Austin III, M.D., cardiovascular and thoracic surgeon, University of Louisville, UofL Physicians - Cardiovascular and Thoracic Surgery; professor and vice-chairman of the Department of Cardiovascular and Thoracic Surgery, UofL School of Medicine

As winner of the provider category, Austin has spent his career as a physician-educator and surgeon treating adults and children in need of congenital heart repairs. The ability to positively impact a person’s health quickly, along with the challenge of cardiovascular and thoracic surgery made the specialty particularly appealing to him.

• Provider Finalist – Christian Davis Furman, M.D., geriatrician, UofL Physicians - Geriatrics; professor of geriatric & palliative medicine; interim chief, Division of General Internal Medicine, Palliative Medicine and Medical Education, UofL School of Medicine; Margaret Dorward Smock Endowed Chair in Geriatric Medicine; medical director, UofL Trager Institute

Furman was recognized as a finalist in the provider category for her work in the field of geriatrics. She still makes home visits and in her Q&A with Business First says the most rewarding part of her job is bringing together patients and families to discuss goals of care and advance care planning.

Read more about the Healthcare Hero finalists and winners on the Business First website.

After learning she had a family history of brain aneurysms, Mary Steinhilber went in for testing to see whether she also had an aneurysm.

Doctors found she had not one, but three. Robert James, M.D., a neurosurgeon at UofL Physicians – Neurosurgery, treated two of her aneurysms with minimally invasive stents, but the location of the third, at a juncture of arteries, was not conducive to stent treatment.

In January, the U.S. Food and Drug Administration (FDA) approved the WEB^® Aneurysm Embolization System for treating this type of aneurysm, and on Feb. 13, Steinhilber was one of the first three patients in Kentucky to be treated with the device at UofL Hospital.

An aneurysm is an enlarged, weakened area of an artery that results in a bulging or ballooned area in the artery. Untreated, an aneurysm in the brain may rupture, causing severe disability, cognitive loss or death. The WEB system, James said, provides a new, minimally invasive option for treating wide-necked bifurcation aneurysms, which occur at the juncture of two arteries. In the procedure, a mesh basket is placed inside the aneurysm, allowing blood to bypass the opening, which seals itself off over time, creating a permanent cure.

“If we can fix the aneurysm before it bursts and cure it, then the threat of this aneurysm bursting and the patient dying from it essentially goes away,” James said. “The WEB device is a game changer for the minimally invasive treatment of aneurysms.”

Steinhilber is grateful to have more advanced options for treating her condition. Two of her sisters were treated for aneurysms in the past. One required re-treatment and another was unable to be treated for one aneurysm due to its location. A third sister died suddenly from what may have been a ruptured aneurysm.

“Seeing the history of my sisters, I feel very good about what the UofL doctors are doing here,” Steinhilber said. “It’s wonderful to see the progress made in treating aneurysms.”

As many as 6 million people in the United States are estimated to have an unruptured brain aneurysm. Coils and stents have provided minimally invasive options for some types of aneurysms, but James explained those options have limitations in their use, and may have negative features.

The WEB (an acronym for Woven Endo-Bridge) device is approved for treating wide-neck bifurcation aneurysms, which may account for 35 percent of all brain aneurysms. James completed the first three procedures in Kentucky with the device since it received FDA pre-market approval on Jan. 7. He had previous experience in performing the procedure, having participated in the device’s clinical trials.

During the WEB system procedure, a small catheter is threaded from the groin area through the patient’s artery to the aneurysm site. Using fluoroscopy imaging, the surgeon deploys the WEB device into the “sack” of the aneurysm, where its flexible mesh conforms to the aneurysm walls, minimizing blood flow inside the aneurysm. In most cases, over time, the body seals off or occludes the neck of the aneurysm, essentially curing it.

In clinical testing, the WEB system was shown to be highly effective and safer than other options. In addition, the minimally invasive nature of the procedure means most patients, including Steinhilber, are able to go home the next day.

In addition to unruptured aneurysms, the WEB system may be used in some cases in which the aneurysm has already ruptured, providing more desirable options for treatment.

“This device also gives us the ability to use flow diversion in already ruptured aneurysms to prevent them from re-rupturing, which we have never been able to do before,” James said.

The WEB system, marketed by MicroVention, Inc., a U.S.-based subsidiary of Terumo and a global neurovascular company, has been used safely in more than 6,000 cases outside the United States as well as clinical studies here and abroad.

Feb. 19, 2019

Jeffrey P. Callen, M.D., professor of dermatology in the Department of Medicine, will receive the Lifetime Career Educator Award from the Dermatology Foundation on March 2 in Washington, D.C. The Dermatology Foundation supports research and education in dermatology and provides funding for young professionals as they begin research careers. Since 1999, the foundation has selected one dermatologist for this award annually. Callen’s award will be presented by Ruth Ann Vleugels, M.D., associate professor of dermatology at Harvard Medical School. Callen was Vleugals’ mentor in a program of the American Academy of Dermatology that pairs senior academicians with junior faculty.

A research team at UofL has discovered that an immune checkpoint molecule they developed for cancer immunotherapy also protects against future development of multiple types of cancer when administered by itself.

The recombinant protein molecule SA-4-1BBL has been used to enhance the therapeutic efficacy of cancer vaccines with success in pre-clinical animal models. It accomplishes this by boosting the effectiveness of CD8⁺ T cells, adaptive immune cells trained to target the tumor for destruction. Surprisingly, when the researchers treated normal healthy mice with SA-4-1BBL alone, the mice were protected when the researchers later exposed them to different types of tumor cells.

“The novelty we are reporting is the ability of this molecule to generate an immune response that patrols the body for the presence of rare tumor cells and to eliminate cancer before it takes hold in the body,” said Haval Shirwan, Ph.D., professor in the UofL Department of Microbiology and Immunology and the UofL Institute for Cellular Therapeutics. “Generally, the immune system will need to be exposed to the tumor, recognize the tumor as dangerous, and then generate an adaptive and tumor-specific response to eliminate the tumor that it recognizes. Thus, our new finding is very surprising because the immune system has not seen a tumor, so the response is not to the presence of a tumor.”

The researchers have determined that the molecule generates a tumor immune surveillance system through activation of what are known as CD4⁺ T cells and innate NK cells, thereby protecting the mice against various cancer types they have never had. This function is an indication of the molecule’s effectiveness in cancer immunoprevention.

In the research, published today in Cancer Research, mice that had never had cancer were treated with SA-4-1BBL alone, then challenged with cervical and lung cancer tumor cells at various time intervals. The mice showed significant protection against tumor development, with the greatest protection when challenged two weeks after treatment with SA-4-1BBL. The cancer immunoprevention effect generated by SA-4-1BBL lasted more than eight weeks.

“Just giving SA-4-1BBL alone prevents the formation of tumors in animal models,” Shirwan said. “To our knowledge, this is the first study to demonstrate that an immune checkpoint stimulator, known for its function for adaptive immunity, as a single agent can activate an immune system surveillance mechanism for protection against various tumor types.”

Additional testing showed that CD8⁺ T cells were not required for the protection, but when CD4⁺ T and NK cells were eliminated in the mice, protection failed, indicating these two cell types were necessary to achieve the effect. The lack of necessity for CD8⁺ T cells indicates the process is not one of conventional acquired immunity.

Although the research, which was conducted in collaboration with FasCure Therapeutics, LLC, tested the mice for cervical and lung cancers, the protective function of SA-4-1BBL works without context of specific tumor antigens, giving it the potential to be effective in preventing any number of tumor types.

“We are very excited about the cancer immunoprevention possibilities of this molecule. Its effectiveness is not tumor specific, and as a natural ligand, it does not cause toxicity, as is found with 4-1BB agonist antibodies. Plus, the fear of autoimmunity is highly minimized, as evident from our data, because it is activating the innate immune cells,” said Esma Yolcu, Ph.D., associate professor at UofL and co-author of the study.

Immune checkpoint stimulators and inhibitors are major regulators of the immune system and work in a similar fashion to the “brake” and “gas” pedals in a vehicle. Cancer evades the immune system by various means, including immune checkpoint inhibitors, which apply the brake on the immune response against a tumor. Stimulators, on the other hand, serve the accelerator function, improving immune responses against cancer.

Drugs to block the action of immune checkpoint inhibitors already have shown therapeutic efficacy for several cancer types in the clinic and are approved by the Food and Drug Administration (FDA). According to Shirwan, the focus now is on immune checkpoint stimulators.

“Several antibody molecules are in clinical testing for cancer immunotherapy as immune checkpoint stimulators. However, nothing so far is approved by the FDA that gives a positive signal to the T cells,” Shirwan said. “The immune checkpoint inhibitors take the foot off the brake, so to speak. This ligand, as an immune checkpoint stimulator, puts the gas on the immune system to destroy the tumor.

“Another big surprise is that an antibody to the same receptor targeted by SA-4-1BBL did not protect against tumors, demonstrating unique and desired features of SA-4-1BBL for caner immunoprevention.”

Shirwan and Yolcu plan to conduct further tests for SA-4-1BBL in cancer immunoprevention.

“Although the notion of cancer immunoprevention is an attractive one, the design of clinical trials presents a challenge with respect to the target population,” Shirwan said. “However, with advances in cancer screening technologies and genetic tools to identify high-risk individuals, we ultimately are hoping to have the opportunity to test the SA-4-1BBL molecule for immunoprevention in individuals who are predisposed to certain cancers, as well as in the presence of precancerous lesions.”

To encourage and accelerate research in cancer prevention, the National Institutes of Health have created a network for research into immunoprevention, outlining possible methods for testing promising preventive substances and provided opportunities for associated funding. The Immuno-Oncology Translational Network is designed to create a fertile environment for research and to facilitate cancer immunoprevention research projects focusing on people who are genetically predisposed to certain cancers, those who have been diagnosed with pre-malignant lesions or polyps, and individuals exposed to cancer-causing substances, such as smokers and asbestos workers.

Feb. 15, 2019

A professional with almost a decade in caring for patients who identify as lesbian, gay, bisexual, transgender, gender non-binary and those born with differences in sex development has been selected to lead the LGBT Center at the University of Louisville Health Sciences Center.

Bláz Bush of New York will join UofL Feb. 25. He brings a skill set particularly attuned to the needs of the LGBT community at the HSC, said Vice Provost for Diversity and International Affairs Mordean Taylor-Archer.

“Bláz combines a wealth of experience in LGBT health care with a collaborative, inclusive leadership style,” Taylor-Archer said. “These qualities make him perfectly positioned to take the HSC LGBT Center to the next level of success in serving our students, faculty, staff, community and ultimately patients.”

Bush comes to UofL after serving as the director of care coordination of the Callen-Lorde Community Health Center, one of the largest LGBT community health centers in the world, serving 18,000 patients annually.

At Callen-Lorde, Bush oversaw 40 case managers, patient navigators and prevention and outreach counselors. He also led the health center in a number of initiatives, including improving community HIV viral-suppression rates and developing interventions to address social determinants of health.

Bush also served on the Health and Human Services HIV Planning Council of New York’s Integration of Care subcommittee, working with city leaders to develop HIV/AIDS programs focused on transgender and non-binary gender health disparities, housing, opioid-use reduction, food and nutrition and care coordination programs.

Prior to Callen-Lorde, Bush was with the New York Blood Center’s Infectious Diseases Research Program. He earned a master’s degree with a focus in community counseling from the University of Oklahoma.

UofL is a leader in the field of educating medical students in the needs of LGBT patients, serving as the pilot program for the Association of American Medical Colleges recommendations to embed training in the care of these patients throughout the medical school curriculum. UofL’s project, eQuality, won the 2016-2017 Innovation in Medical Education Award from the Southern Group on Educational Affairs.

“The work being done at the University of Louisville to educate future generations of health care providers in lesbian, gay, bisexual and transgender and gender non-binary health care needs is essential, lifesaving and radical,” Bush said. “Having worked at an LGBT health center, I understand the vital importance of adequate training and the desperate need for sensitive, quality health care to be widespread and accessible for all communities, especially for communities of color.

“The University of Louisville is already the leader in creating an LGBT-inclusive campus and is an innovator in creating LGBT educational programs. I am humbled and excited for this opportunity to help lead the Health Sciences Center forward and continue its progressive leadership in educating the caregivers of tomorrow.”

Individuals living with Parkinson’s disease, along with their families and caregivers, will have the opportunity to hear from a popular author and expert on the treatment of Parkinson’s, J. Eric Ahlskog, M.D., Ph.D., at the annual Bill Collins Symposium for Parkinson’s Disease. The annual symposium also will include care insights for patients, families and caregivers by the providers of UofL Physicians – Parkinson’s Disease and Movement Disorders clinic.

The half-day event is Saturday, March 2, from 8:30 a.m. to 12:15 p.m. in the conference center of the Rudd Heart and Lung Building, 201 Abraham Flexner Way, next to Jewish Hospital. There is no charge to attend.

Ahlskog, professor of neurology at Mayo Clinic Alix School of Medicine, is the author of “The New Parkinson’s Disease Treatment Book,” a popular guide for people with Parkinson’s disease and their families. He will give the keynote talk for the symposium, “Debunking Ten Myths that May Sabotage Treatment of Parkinson’s Disease.”

In addition, Karen Robinson, Ph.D., F.A.A.N., of the UofL School of Nursing, will discuss the importance of support for caregivers, and Robert Friedland, M.D., professor and researcher in the Department of Neurology at UofL, will explain the impact of the microbiome in Parkinson’s disease and dementia. Finally, a panel discussion will include providers from the UofL Physicians – Parkinson’s Disease and Movement Disorders clinic.

“We have organized this opportunity to allow patients and their families to meet one another and to learn about the best ways to manage the journey of Parkinson’s disease,” said Kathrin LaFaver, M.D., director of the UofL Physicians – Parkinson’s Disease and Movement Disorders clinic and the Raymond Lee Lebby Chair in Parkinson’s Disease Research at the University of Louisville School of Medicine. “This year, they will have a unique chance to hear from Dr. Ahlskog, a renowned expert in Parkinson’s care. We also will introduce a caregivers’ support group, which will begin in March.”

Parkinson’s disease caregiver support group

Caring for a partner or family member with Parkinson's disease has many rewards, but also has been associated with physical, mental, social and financial stressors. Beginning in March, the UofL Physicians – Parkinson's Disease and Movement Disorders clinic will offer a monthly caregiver support group led by Kelly Bickett, a registered nurse in the movement clinic with special expertise in the care of Parkinson's disease. To facilitate attendance at support group meetings, respite care will be made available on an as-needed basis through a professional health-care agency for up to four hours. 

The group will begin Friday, March 29, and meet the fourth Friday of each month from 2:30 - 4:00 p.m. Register for the support group by calling 502-582-7654.

Bill Collins Symposium for Parkinson’s Disease agenda

• Keynote: “Debunking Ten Myths that May Sabotage Treatment,” by J. Eric Ahlskog, M.D., Ph.D.
• Active Break:  Dance for Health – David X. Thurmond, professional dancer, choreographer and teacher.
• Microbiome in Parkinson’s disease and dementia - Robert P. Friedland, M.D., UofL Department of Neurology and the Mason C. and Mary D. Rudd Endowed Chair in Neurology.
• Supporting caregivers of those with Parkinson’s disease – Karen Robinson, Ph.D., F.A.A.N., UofL School of Nursing.
• Panel discussion with Ahlskog and Kathrin LaFaver, M.D., along with Victoria Holiday, M.D., UofL Department of Neurology and Laura Dixon, D.N.P. A.P.R.N., UofL Physicians – Parkinson’s Disease and Movement Disorders.

There is no charge to attend the symposium, but please register by Feb. 25 by calling 502-582-7654 or via email to UofLPhysiciansMovement@ulp.org. Please include your name, the number of guests attending and a telephone number.

February 7, 2019

A number of potentially life-threatening toxins found in many households can seriously harm your furry best friend. Even things humans safely ingest every day can be fatal to pets.

At the next Beer with a Scientist, Kate Baker, D.V.M., M.S., a veterinary clinical pathologist with Blue Pearl Specialty and Emergency Veterinary Hospital, will explain why some seemingly harmless substances actually are very dangerous for our animals. She also will address what veterinarians do to save pets when they ingest a toxin.

"Many of us share our homes with pets, and sometimes, they eat things they shouldn’t. While some of these things may be harmless, others can seriously harm pets, even things people consume every day with no issues, from common medications such as Tylenol or ibuprofen, to foods we eat every day like onions and grapes,” Baker said.

Baker’s talk will begin at 7 p.m. on Wednesday, Feb. 13, at Holsopple Brewing, 8023 Catherine Lane, Louisville, 40222. A 30-minute presentation will be followed by an informal Q&A session.

Admission is free. Purchase of beer or other items is not required but is encouraged.

Organizers encourage Beer with a Scientist patrons to drink responsibly.

UofL cancer researcher Levi Beverly, Ph.D., created the Beer with a Scientist program in 2014 as a way to bring science to the public in an informal setting. At these events, the public is invited to enjoy exactly what the title promises:  beer and science.

Upcoming Beer with a Scientist dates:  March 13, April 17, May 15.

February 7, 2019