A University of Louisville-born startup using innovative personalized cell therapies to help patients with pancreatitis and other conditions has been acquired by publicly traded biotech company, Orgenesis Inc. (NASDAQ: ORGS) in a roughly $15 million deal.

The startup, Koligo Therapeutics Inc., led by a UofL alumnus, was launched in 2016 to develop and commercialize UofL research and technology for personalized therapies using a patient’s own cells. One UofL-developed therapy for pancreatitis already is on the market and another for COVID-19-related acute respiratory distress soon will enter a multi-site phase 2 clinical trial led by UofL.

“These therapies have come a long way since that first ‘eureka’ moment in the lab at UofL,” said Stuart K. Williams II, Ph.D., a professor in the UofL Department of Physiology who co-invented the technologies, co-founded Koligo and now serves as its chief technology officer. “This acquisition supports expanded treatment of chronic pancreatitis patients and could further our cell-based treatments for COVID-19 patients throughout the United States.”

The first therapy originated in UofL’s islet transplant program with co-inventors Williams, Michael Hughes, M.D., and Balamurugan Appakalai, Ph.D., with early grant funding from the Jewish Heritage Fund for Excellence. This therapy is now marketed as Kyslecel ™ to treat chronic and recurrent acute pancreatitis, which can cause pain, inflammation and diabetes as the pancreas degrades. The technology is available today in six U.S. hospitals and so far has been used to treat 38 patients.

In the Kyslecel therapy, a surgeon removes the diseased pancreas and sends it to Koligo where the islets are extracted and preserved to make Kyslecel. The drug is then returned to the patient’s health care facility to be infused into the liver where the islets are expected to function and produce the insulin needed to regulate blood sugar. Williams said the goal for the next generation of islet cell therapies will be to deliver the islets via implant created using 3D-V, a UofL-developed bioprinting technology. 

Koligo plans to test another therapy, KT-PC-301, in treating COVID-19-related acute respiratory distress syndrome (ARDS) in a forthcoming multi-site phase 2 randomized clinical trial, pending FDA review and clearance of an Investigational New Drug application.

The planned trial, led by Mohamed Saad, M.D., chief of the UofL Division of Pulmonary, Critical Care and Sleep Disorders Medicine, is expected to enroll 75 COVID-19 patients. A list of other ongoing clinical trials at UofL is available here.

ARDS can occur in critical cases of COVID-19 when the lungs swell and fill with fluid as the body tries to fight off the infection. KT-PC-301 is a cell therapy that is derived from a patient’s own fat tissue. A small amount of fat is collected from the patient and sent to Koligo to make KT-PC-301. The product is manufactured within hours and sent back to the hospital for intravenous administration. KT-PC-301 then migrates to the patient’s lungs to reduce inflammation.

UofL licensed the Kyslecel and 3D-V technologies exclusively to Koligo through the UofL Commercialization EPI-Center, which works with startups and industry to commercialize research-born technology. Those licenses transfer to Orgenesis. UofL also maintains an equity stake in Koligo which has become an equity stake in Orgenesis after closing of that transaction.

“We look forward to continuing our strong relationship with UofL, now with an even wider reach and global scale,” said Koligo Chief Executive Officer Matthew Lehman, who also is a former UofL McConnell Scholar and political science and history alumnus. “Together, Orgenesis and UofL will further develop these therapies that have real potential to save lives.”

Courtney Schadt, M.D., of the UofL School of Medicine has been named to the Board of Directors of the Association of Professors of Dermatology. The APD is the primary professional organization in the United States focused on the promotion of medical education, research and patient care, particularly in undergraduate and graduate dermatology training programs.

Schadt is an associate professor in the UofL Division of Dermatology, part of the Department of Medicine and a Fellow of the American Academy of Dermatology.

In addition to her clinical duties, Schadt serves as the chief of dermatology at the Robley Rex Veterans Affairs Medical Center and director of the Dermatology Residency Program and clerkship director for the Medical Student Rotation in Dermatology in the School of Medicine.

Southside residents now have increased access to crucial addiction recovery services at UofL Health – Mary & Elizabeth Hospital’s new voluntary medical detox unit. Mary & Elizabeth Hospital has partnered with UofL Health – Peace Hospital to create the unit, which will be staffed with medical personnel and therapists specifically trained to treat behavioral health issues and addiction.

While detox services have long been offered at Mary & Elizabeth Hospital, the new dedicated unit allows for specialized care team to better monitor health and vital signs throughout the detox process to prevent dangerous symptoms from occurring. The team also will offer therapy groups and licensed therapists who will assist with discharge planning and aftercare services to ensure patients maintain their treatment plans to achieve long-term sobriety and increased well-being. In addition, art and music will be incorporated into support groups and guided meditation.

“The neighborhoods that encompass Mary & Elizabeth Hospital and the surrounding area experience a disproportionate amount of opioid addictions and overdoses,” said Melisa Adkins, chief administrative officer at Mary & Elizabeth Hospital. “This new detox unit will help those who suffer take the initial steps to help conquer their addiction in a convenient, supportive and safe environment.” 

Mary & Elizabeth Hospital will initially staff 12 private-bed rooms, but has the capacity to care for up to 25 patients. The unit will specialize in those detoxing off various substances such as EtOH (ethanol/alcohol abuse), opiates and benzodiazepines that may also have a comorbidity or medical complication. Referrals are expected from the Mary & Elizabeth emergency department and Peace Hospital, across UofL Health, as well as from various other emergency departments or freestanding psychiatric facilities in the Louisville area.

At discharge, a therapist/case manager will work with each individual patient to assess future needs, including community resources, placement at a long-term rehab facility and continued therapy. Just across the street, Peace Hospital offers a full complement of adult outpatient services, including specialized treatment methods with motivational interviewing, group therapy and 12-step facilitation. The program focus is on adults 18 years or older, and additional support is available such as transportation and six months of free after-care.

In addition to the voluntary medical detox unit, both Mary & Elizabeth Hospital and Peace Hospital offer long-acting injection (LAI) clinics, which provide monthly shots of long-acting medications to help patients with opioid addiction and schizoaffective disorders. Some patients will be able to have orders issued from Mary & Elizabeth physicians to receive LAI injections immediately after discharge from the detox unit but before leaving campus to assist in their ongoing recovery.

“Addiction to opioids, alcohol or any other substance is a concerning medical issue — not a moral failing — and these patients need ready access to knowledgeable, compassionate care,” said Jeff Graves, M.D., chief medical officer at Mary & Elizabeth Hospital. “By increasing access to these services to the most vulnerable populations in the area, we are doing our part to help set them up for long-term success.”

For more information regarding Mary & Elizabeth’s voluntary detox unit, please visit: www.uoflhealthnetwork.org/inpatient-medical-detox.

Cancer remains one of the most difficult and deadly challenges in human health, affecting Kentuckians at a higher rate than residents of any other state and killing more than 600,000 people each year in the U.S. alone. In recent decades, therapies that engage the immune system to treat cancer have given hope to millions of cancer patients.

Building on more than two decades of success in cancer research, the University of Louisville is poised to advance immunotherapy with a grant of $11.5 million from the National Institute of General Medical Sciences to establish the Center for Cancer Immunology and Immunotherapy (CCII). The new center will develop and improve strategies that use the immune response to fight cancer. The five-year grant also will allow UofL to establish the CCII as a National Institutes of Health-designated Center of Biomedical Research Excellence (CoBRE) to support young investigators and develop additional basic, translational and clinical research at the UofL Health – James Graham Brown Cancer Center.

“One of the university’s Grand Challenges is to advance the health of all people,” said UofL President Neeli Bendapudi. “Through this center, our cancer researchers will grow the field of immunotherapy, saving the lives of many more patients with cancer in the future.”

“Our mission is to harness the power of the immune system to eradicate cancer,” said Jason Chesney, M.D., Ph.D., director of the Brown Cancer Center. “The University of Louisville, UofL Health and the Brown Cancer Center have been at the forefront of the clinical development of a new generation of immunotherapies that have been proven to increase the survival of cancer patients. This grant from the federal government leverages our existing strengths in cancer immunology and clinical trials to accelerate the development of new immunotherapies that will translate into lives saved across the globe."

Cancer survivor Jeff Habermel received two different immunotherapies at Brown Cancer Center in the course of treatment for three different cancers, including metastasized melanoma.

“I consider myself very fortunate to have the type of care that Dr. Chesney and Dr. (Donald) Miller and the whole staff provide at the Brown Cancer Center. We have a world-class facility right in our backyard,” Habermel said. “I truly feel I am the luckiest man in the world to live in a time when we have such technologies and such amazing abilities to treat cancer in these ways.”

The newest cancer treatments often are available at Brown Cancer Center through clinical trials before they are available anywhere else. One such treatment is CAR T-cell therapy, in which a patient’s own immune cells known as T cells are modified in the lab to more effectively attack cancer cells. UofL announced the creation of the Dunbar CAR T-Cell Program at UofL in October.

“Our leading-edge cancer program improves access for patients in our region, giving them the opportunity to benefit from life-saving immunotherapies through clinical trials,” said Tom Miller, CEO of UofL Health. “Thousands of our cancer patients – our neighbors and family members – are alive today because of this early focus on drugs that activate immunity against cancer.”

Researchers within the CCII will build on expertise and resources gained from previous research at UofL to develop better cancer immunotherapies. This will be achieved in part by enabling talented junior investigators who have not yet obtained major funding to advance their research and subsequently obtain major grant awards of their own.

“One of the major goals of the center is to cultivate the next generation of cancer scientists in immunology and immunotherapy,” said Jun Yan, M.D., Ph.D., professor, director of the CCII and chief of the UofL Division of Immunotherapy. “Starting in year two, we will call for pilot projects that will bring in more researchers and investigators to work on immunotherapy and immunology.”

The young researchers are provided funding, mentorship and access to sophisticated facilities to advance their research. Once CCII-supported researchers obtain their own funding they rotate out, allowing new investigators to come in to the program.

“It’s training a cohort of new investigators who will have their own large grants and expertise,” said Paula Bates, Ph.D., professor of medicine and co-investigator for the CCII along with John Trent, Ph.D. “We are building a critical mass of well-funded researchers in the area.”

Senior UofL faculty members Robert Mitchell, Ph.D., Nejat Egilmez, Ph.D., Haribabu Bodduluri, Ph.D., Huang-Ge Zhang, Ph.D., and Bing Li, Ph.D., will serve as mentors and core directors for the CCII. In the first year of the program, four junior researchers at UofL are conducting projects to improve the effectiveness of immune therapies.

• Chuanlin Ding, Ph.D., is investigating the impact of chemotherapy on anti-tumor immunity in breast cancer order to discover effective combination regimens that improve conventional chemotherapy.

• Qingsheng Li, Ph.D., is exploring a method to improve immune checkpoint inhibitor therapy for non-small cell lung cancer. Immune checkpoint inhibitors are a type of immunotherapy that blocks proteins (checkpoints) made by immune system cells, such as T cells. The checkpoints can prevent T cells from attacking cancer cells.

• Corey Watson, Ph.D., is studying immune cells to determine which of these cells are beneficial to lung cancer patient outcomes and how they may help kill tumor cells.

• Kavitha Yaddanapuddi, Ph.D., is studying immune checkpoint inhibitor resistance in lung cancer patients. This will help in developing therapies that reduce resistance and improve treatment.

This grant may be extended for two additional five-year phases. A previous CoBRE program for cancer research at UofL was extended through all three phases, lasting 15 years. That program significantly expanded the contingent of both junior and senior investigators at UofL, including Chesney, Trent and others whose research was funded by the previous program.

“This type of funding has been truly transformative for this cancer center,” Trent said. “The research for the current generation of immunotherapeutic checkpoint inhibitors was done more than 18 years ago. This grant’s research will feed into the clinical work in time. These grants lay the groundwork for the next generation of therapies.”

To extend the impact of the CCII still further, Kosair Charities has provided an additional $200,000 to facilitate the discovery and development of immunotherapy drugs for children with cancer. This gift bridges the CCII and the UofL Kosair Charities Pediatric Oncology Research Program, allowing the CCII to focus also on immuno-oncology for children.

“Kosair Charities is proud to be the first community partner to support the UofL Center for Cancer Immunology and Immunotherapy,” said Kosair Charities President Keith Inman. “The UofL Kosair Charities Pediatric Cancer Research Program will allow this new center to include crucial pediatric cancer research as well as expand the scope to all people living with cancer – children and adults alike.”

Sept. 14, 2020

J. Christopher States, PhD, professor of pharmacology & toxicology, distinguished university scholar, vice chair for research in the department of pharmacology and toxicology and associate dean for research in the School of Medicine, has been awarded the UofL 2020 Distinguished Faculty Award in the category of Outstanding Scholarship, Research and Creative Activity. Professor States’ research is funded by two research project grants from the National Institute of Environmental Health Sciences (NIEHS). He also leads the team that recently received an NIEHS Core Center grant that funds the Center for Integrative Environmental Health Sciences. Read more about professor States’ outstanding scholarship, research and creative activity.

Scott Whittemore, PhD, professor, distinguished university scholar and vice chairman for research in the School of Medicine has been awarded the UofL 2020 Distinguished Faculty Award in the category of Outstanding Scholarship, Research, and Creative Activity (Career Achievement). Professor Whittemore joined the faculty in Neurological Surgery at the University of Miami in 1986 as one of the founding scientists of the newly formed Miami Project to Cure Paralysis. In 1998, he was recruited to the University of Louisville Department of Neurological Surgery as the Henry D. and Marianna Garretson Endowed Professor of Spinal Cord Injury Research. Dr. Whittemore holds a secondary faculty appointment in pharmacology & toxicology. Read more about professor Whittemore’s distinguished research career.  

The James Graham Brown Cancer Center is excited to announce the first Junior Investigator Fellowships. 

 These fellowships are designed for early stage research investigators in Immuno-Oncology.

The Junior Investigator Fellowships are made possible by the Lindy and Bill Street Gift to the JGBCC supporting a proposed Department of Cancer Biology and Medicine. The “Street Fellows” will be talented junior investigators with a strong interest in Immuno-Oncology.  The goal of these awards is for the junior investigator to develop a project so that it and the investigator would be a suitable Project candidate for the BCC COBRE Center for Cancer Immunology and Immunotherapy.

Please see the RFP for details, which is attached to this story.

Questions may be addressed to Diane Konzen at diane.konzen@louisville.edu .

UofL medical faculty leaders have pledged $50,000 toward a $1 million goal to address long-standing racial inequities in medical education.

The University of Louisville School of Medicine’s Endowed Excellence Fund for Diversity has been established by several department chairs to address systemic racism. This is in response to UofL President Neeli Bendapudi’s challenge asking for ideas and support in making UofL the nation’s premier anti-racist metropolitan research university.

"I am proud and deeply grateful for the leadership of these faculty who are using their philanthropic and other financial resources to create a fund that will promote diversity at the School of Medicine both now and for the future," said Toni Ganzel, M.D., M.B.A., dean of the School of Medicine.

The endowment has been established by: 

• Sean Francis, M.D., M.B.A., chair of Obstetrics, Gynecology & Women’s Health
• Ronald Gregg, Ph.D., chair of Biochemistry and Molecular Genetics
• William Guido, Ph.D., chair of Anatomical Sciences & Neurobiology
• Irving Joshua, Ph.D., chair of Physiology
• Maureen McCall, Ph.D., professor of Ophthalmology and Visual Sciences
• Craig S. Roberts, M.D., M.B.A., chair of Orthopaedic Surgery

"This might have more impact at UofL than anything else I have done," Gregg said.

The endowment is expected to be used for scholarships, resident stipends, faculty recruitment and retention packages and other unforeseen opportunities. A dean-appointed selection committee composed of diverse members of the School of Medicine faculty, staff and students will help guide spending decisions.

To learn more about UofL’s anti-racism agenda and diversity efforts, please visit the following websites:

• UofL’s Cardinal Anti-Racist Agenda
• UofL School of Medicine Office of Community Engagement and Diversity
• HSC Office of Diversity and Inclusion
• UofL Office of Diversity and Equity
• Commission on Diversity and Racial Equality

Consider making a gift using the secure online giving page, follow give.louisville.edu/eefd.

Faculty and staff have the option to make contributions by payroll deduction to "UofL Endw Excellence Diversity" Click here for instructions for setting up payroll deduction through ULink. 

For questions or to establish a multi-year pledge, please contact University Advancement at 502.852.2794.

The emergence of the SARS-CoV-2 pandemic has caused tremendous upheaval throughout the world, leading to extensive efforts to reduce transmission of the virus and cases of the disease it causes, COVID-19, resulting in significant economic disruption.

Since warmer weather is known to decrease the transmission of other coronaviruses, researchers at the University of Louisville’s Christina Lee Brown Envirome Institute, the Johns Hopkins University School of Medicine and the U.S. Department of Defense Joint Artificial Intelligence Center theorized that atmospheric temperature also would affect transmission of SARS-CoV-2. To find out, they compared temperature data and logged cases of COVID-19 in 50 countries in the Northern Hemisphere between Jan. 22 and April 6.

The data showed that as temperatures rose, the rate of increase in new cases of COVID-19 decreased.

“Although this is typical and expected behavior for most members of the coronavirus family, SARS-CoV-2’s rapid spread and lethality have been atypical and unexpected. The confirmation of the SARS-CoV-2 temperature sensitivity has important implications for anticipating the course of the current pandemic,” said Adam Kaplin, M.D., Ph.D., of Johns Hopkins, an author of the study.

The researchers compared daily low temperature and relative humidity data with logged COVID-19 cases in the 50 Northern Hemisphere countries. The data showed that between 30 and 100 degrees Fahrenheit, for every 1 degree Fahrenheit increase in temperature, COVID-19 cases declined by 1%, and for every 1 degree decrease in temperature, cases would be predicted to rise by 3.7%.

“Of course, the effect of temperature on the rate of transmission is altered by social interventions like distancing, as well as time spent indoors and other factors. A combination of these factors ultimately will determine the spread of COVID-19,” said Aruni Bhatnagar, Ph.D., co-author and director of the Brown Envirome Institute.

In the United States, sharp spikes in COVID-19 have been seen over the summer, but the researchers noted that based on the data they analyzed, cooler summer temperatures may have resulted in an even higher number of cases.

“Although COVID-19 is an infectious disease that will have non-temperature dependent transmission, our research indicates that it also may have a seasonal component,” Bhatnagar said. “This means that this winter could bring a serious surge on top of the regular transmission.”

The research, Evidence and magnitude of seasonality in SARS-CoV-2 transmission: Penny wise, pandemic foolish?, published as a preprint on MedRxiv, also indicates that the correlation between temperature and transmission was much greater than the association between temperature and recovery or death from COVID-19.

Sept. 1, 2020

Fatty acid binding proteins (FABPs) serve as a type of chaperone, coordinating the transport of fatty acids and other molecules between cells. Bing Li, Ph.D., associate professor in the Department of Microbiology and Immunology at the University of Louisville and a leading researcher in understanding the role of FABPs, has created a “SnapShot” of the functions of these proteins published in the journal Cell, a highly regarded scientific journal covering cell biology.

At least nine types of FABPs, identified by the tissues and organs in which they were first discovered, are known to have numerous roles in lipid metabolism. While they are responsible for important functions in maintaining health, obesity can result in higher levels of these proteins, igniting disease.

“When people are obese, FABPs in different cells and tissues are upregulated, resulting in changes in lipid metabolism and responses,” Li said.

Li’s research focuses the role of FABPs in chronic inflammation, obesity and cancer development. He recently published a proposed mechanism for how increased levels of one of these proteins, FABP4, resulting from higher amounts of fat tissue, promote breast tumor growth.

“Studies from my laboratory demonstrate that FABP family members, especially FABP4 and FABP5, are critical in mediating obesity-associated diseases by regulating immune cell functions,” Li said. “Thus, our studies on FABPs not only uncover the underlying mechanisms by which obesity undermines human health, but also provide new targets for novel immunotherapeutic strategies for clinics.”

Editors of the journal Cell invited Li to create the SnapShot to illustrate the functions of all known FABPs in health and disease with an emphasis on their role in obesity, chronic inflammatory disease and cancer. SnapShots are graphic diagrams designed to serve as quick reference guides for researchers on a specific topic.

“The SnapShot format offers a great deal of opportunity for creativity and can be printed and pinned above lab benches to jog researchers’ memories,” Li said. “While our studies open a window to see the important functions of FABP family members in some disease contexts, a lot of questions remain unexplored in this field. I hope this piece will encourage more young scientists to contribute their talents to combat obesity and obesity-associated diseases.”

Aug. 20, 2020

The Department of Pharmacology and Toxicology is pleased to announce that Jeffrey Warner is the fourth graduate student in the pharmacology and toxicology program this year awarded an individual predoctoral fellowship.  Three of the awards are Ruth L. Kirschstein Predoctoral National Research Fellowship Awards (F31) from the National Institutes of Health.  The fourth predoctoral fellowship was awarded by the non-profit foundation Autism Speaks.  Two of these graduate students (Sarah Shrader and Jeffrey Warner) previously were awarded predoctoral fellowships on the NIH funded T32 training grant in environmental health sciences.

The Department of Pharmacology and Toxicology and the NIEHS T32 training program in environmental health sciences are very proud of the success of these graduate students and their mentors in receiving extramural predoctoral fellowships for their PhD dissertation studies.  The graduate students and their mentors are listed below:

Jeffrey Warner, NIH F31 predoctoral fellowship entitled “sEH Inhibition in Alcoholic Liver Disease: A Novel Therapeutic Strategy”.  His mentor is Dr. Irina Kirpich.

Mengwei Jiang NIH F31 predoctoral fellowship entitled “Probiotic and intestinal miR194 regulation of bile acid metabolism in alcoholic liver disease”.  His mentor is Dr. Wenke Feng.

Sophie Sears NIH F31 predoctoral fellowship entitled “Role of macrophages in cisplatin-induced kidney injury and progression to chronic kidney disease”.  Her mentor is Dr. Leah Siskind.

Sarah Shrader, Autism Speaks predoctoral fellowship entitled “Phytocannabinoids as behavioral and immunological modulators in autism spectrum disorders”.  Her faculty mentors are Drs. Zhao-hui Song and Gregory Barnes.

Jeff Warner        Sarah Shrader      Sophie Sears          Mengwei Jiang

Mary Nan S. Mallory, M.D., M.B.A., has been elected president of the American Board of Emergency Medicine (ABEM). Mallory is vice dean for clinical affairs for the University of Louisville School of Medicine, a professor in the Department of Emergency Medicine and an attending physician at UofL Health - UofL Hospital.

Mallory has been a member of the ABEM Board of Directors since July 2012 and was elected to the Executive Committee in 2019. She has served ABEM as chief examiner and editor for the Oral Certification Examination and co-editor of the In-training Examination, as well as secretary-treasurer and chair of the Finance, Bylaws and Continuing Certification committees.

"I look forward to my role as ABEM president and continuing conversations with diplomates and candidates, navigating certification examination transitions and ensuring certification standards and value as we move through these challenging times together" Mallory said.

Mallory received her medical degree from the Joan C. Edwards School of Medicine at Marshall University and completed residency training in emergency medicine at UofL. She also earned an M.B.A. from UofL College of Business.

August 10, 2020

Mike Onu Udoh, a second-year UofL medical student, has been appointed vice chair of the Minority Issues Committee in the American Medical Association’s Medical Student Section. The standing committee charged with addressing issues of concern to minority populations through policy development, health education and service, as well as identifying minority student needs and ways to increase membership awareness and knowledge of minority issues.

Udoh also is president of the American Medical Association/Kentucky Medical Association chapter at University of Louisville and the health care representative for the class of 2023 in the School of Medicine Student Government.

August 8, 2020

The third cohort of the Leadership and Innovation in Academic Medicine (LIAM) program completed an 11-month course to develop faculty leaders by presenting their projects designed to improve academic work or health care at the University of Louisville. LIAM is one of the most popular programs offered by the HSC Office of Faculty Development.

The 25 members of the class of 2019-2020, organized in five teams, outlined plans for improving faculty research productivity, patient access, employee recognition, communication and active learning in July. This was the first LIAM class to include faculty from the Belknap Campus.

The mission of the LIAM program is to develop the next generation of leaders at UofL by teaching them the skills needed first to lead themselves, then lead with others and finally, lead an organization. Faculty members enroll in an 11-month training program that includes regular discussions and the capstone team projects.

“Leadership is a set of skills that you can practice. It’s not something you are born with or not born with, but there is a set of definable skills, and with any skill, if you practice it, you get better at it,” said Gerard Rabalais, M.D., M.H.A., who developed and directs the LIAM program with Staci Saner, M.Ed.

LIAM originally was designed as a program for faculty in the School of Medicine, but has evolved quickly to include faculty members across the university.

“Our five-year goal is for 15 percent of the faculty at the Health Sciences Center campus to complete this program. Once you get to that tipping point, synergy is going to start to kick in,” Rabalais said. “That is the result of the cross-disciplinary relationships that develop, meeting and working with people they would never have worked with before from different departments or across colleges. Now that we have increased interest from faculty on the Belknap Campus, with 16 people completing the program by July 2021, we likely will set the same target for Belknap Campus.”

During the event, the program’s fourth cohort of 40 faculty members was introduced. It is the largest class in the program’s history and includes 11 members from Belknap Campus and 9 from Health Sciences Center schools other than the School of Medicine.

Projects and team members in the LIAM class of 2019-2020:

Improving Faculty Research Productivity:
David Brown, Ph.D., Linda Fuselier, Ph.D., Brandon McCormack, Ph.D., Susan Ryan, Ph.D., Siobhan Smith-Jones, Ph.D.

Patient Access at UofL Physicians:
Jennifer Daily, M.D., Luz Huntington-Moskos, Ph.D., Marija Sasek, D.M.D., Maria Mendoza, M.D., Rodolfo Zamora, M.D.

Employee Recognition:
HimaBindu Dukka, B.D.S., M.S.D., M.P.H., Arpita Lakhotia, M.D., W. David Lohr, M.D., Suzanne McGee, M.D., Michael Sweeney, M.D.

Communication:
Brit Anderson, M.D., Tamer Mohamed, Ph.D., Kimberly Pate, M.D., William Tse, M.D., Ph.D.

Driving Active Learning:
Michael Egger, M.D., James Harrison, D.M.D., Chithra Ram, M.D., Jennifer Stiff, M.D., Tracy VanMeter, M.D., Beverly Williams-Coleman, D.N.P., A.P.R.N., FNP-C

LIAM program class of 2020-2021:

• Jason Gainous, PhD                                              Arts & Sciences
• Kandi Walker, PhD                                                Arts & Sciences
• Regina Roebuck, PhD                                            Arts & Sciences
• Benjamin Mast, PhD, ABPP                                  Arts & Sciences
• Kevin Gawley                                                        Arts & Sciences
• Dawn Heinecken, PhD                                          Arts & Sciences
• Amy Flint, PhD, MEd                                             Education and Human Development
• Douglas Craddock, PhD                                        Education and Human Development
• Andrew McCart, PhD, MBA                                  Education and Human Development
• Ishwanzya Rivers, PhD                                          Education and Human Development
• Brigitte Burpo, PhD, MEd                                     Education and Human Development
• Jill Steinbach-Rankins, PhD                                  Speed School of Engineering
• Matthew Fox, MD                                                 Medicine
• Adam Ross, MD                                                    Medicine
• Ashley Iles, MD                                                     Medicine
• April Herrity, PhD                                                  Medicine
• Beatrice Ugiliweneza, PhD                                   Medicine
• Timothy Ford, DPM                                               Medicine
• Siddharth Shah, MD                                             Medicine
• Becca Hart, MD                                                     Medicine
• Kelly Jackson, MS                                                  Medicine
• Sunnye Mayes, PhD                                              Medicine
• Jeff Meyer, MD                                                     Medicine
• Courtney Smith, PhD                                            Medicine
• Joshua Sparks, MD                                                Medicine
• Rebecca Starr Seal, DO                                         Medicine
• Amanda LeBlanc, PhD                                           Medicine
• Leslie Sherwood, DVM                                          Medicine
• Samuel Carson, MD                                              Medicine
• Clayton Tyler Ellis, MD                                          Medicine
• Kellen Choi, DO                                                     Medicine
• Cynethia Bethel-Jaiteh, DNP, APRN, CPNP, CLC   Nursing
• Muna Hammash, PhD, RN                                    Nursing
• Imelda Wright, PhD, RN, CNOR                            Nursing
• J'Aime Jennings, PhD                                            Public Health and Information Sciences
• Brian Marrillia, DMD                                             Dentistry
• Lavina Myers                                                         Dentistry
• Juhi Bagaitkar, PhD                                               Dentistry
• Gill Diamond, PhD                                                Dentistry
• Ashley King-Tinsley, DMD                                     Dentistry

A University of Louisville-born therapy that helps people with Type 1 diabetes stay off immunosuppressants by re-educating the body’s immune system to accept transplanted insulin-producing cells now has a commercial partner.

iTolerance Inc., a San Mateo, Calif.-based biotech company, has signed an exclusive license and intends to develop the therapy toward clinical use. The technology was co-invented at UofL and at the Georgia Institute of Technology with support from the National Institutes of Health and JDRF, which funds Type 1 diabetes (T1D) research.

“Our goal is to help people with Type 1 diabetes, so they don’t have to suffer the side effects that come with immunosuppressants,” said Haval Shirwan, Ph.D, inventor and gratis professor in the UofL Department of Microbiology and Immunology.

In Type 1 diabetes, a condition affecting some 1.6 million Americans, the body’s immune system attacks cells in the pancreas that produce insulin, a hormone that regulates blood sugar. As a result, patients that receive pancreatic islet transplants need to be placed on immunosuppressants and cope with the possible side effects, including loss of appetite, nausea and increased risk of infection.

The technology works by training the immune system to accept insulin-producing cells through transplanted islets — cells taken from the pancreas. The islets are laced with a recombinant protein pioneered by Shirwan and Esma S. Yolcu, Ph.D., a gratis faculty member at UofL, known as Fas ligand (FasL), which “teaches” the immune system to see new graft as beneficial rather than a threat.

Once the immune system has been re-trained, the idea is to transplant healthy islet cells so the patient again can produce insulin on their own.

The UofL scientists teamed up with researchers at Georgia Tech to generate a hydrogel formulation delivering FasL to the graft site to ward off rejection. The technology has the potential to be an “off-the-shelf” treatment, and the hydrogels which hold the islets can be prepared up to two weeks ahead of the transplant. The islets also don’t need to be modified for the individual patient.

“We look forward to leveraging the technology to locally and durably induce immune tolerance of organ transplants,” said Cameron Gray, Ph.D., J.D., founder and chairman of iTolerance. “We believe the technology has potentially far-ranging implications for engraftment."

iTolerance holds an exclusive license to the technology through Georgia Tech and the UofL Commercialization EPI-Center, which works with startups and industry to commercialize university-born technologies.

IMAGE: Immunomodulatory signal presentation via synthetic hydrogel material promotes generation of T regulatory cells (green) in the local graft microenvironment (CD3+ T cells in red, and nuclei staining in blue) after implantation into a clinically relevant transplant model for the treatment of Type 1 diabetes. (Image courtesy Georgia Tech)

August 6, 2020

Amid efforts to stem the spread of the COVID-19 pandemic, social isolation and loneliness have emerged as a significant public health crisis, particularly for older adults. Isolation and loneliness affect those living in facilities as well as those living on their own in the community.

In addition to the mental health implications such as depression, studies gathered by the National Institute on Aging demonstrate that prolonged social isolation can lead to other health complications, including cognitive decline, high blood pressure, heart disease and a weakened immune system. These side effects are particularly concerning during COVID-19 when such comorbid conditions put individuals at higher risk for adverse reactions from the virus. 

The University of Louisville Trager Institute is developing technologies and services to reduce social isolation while maintaining social distancing. 

“Social distancing does not have to mean social isolation,” said Anna Faul, Ph.D., executive director of the UofL Trager Institute. “We are working with community partners to bring technology and social supports to older adults facing increased social isolation due to the current pandemic.”

In April, for example, the UofL Trager Institute and Brent Wright, M.D., of the UofL School of Medicine, introduced SmartGlasses technology to long-term facilities and primary care offices. This technology allows a health care professional who is with the patient to put on the web-connected glasses and dial in with an attending physician. A camera and microphone attached to the glasses allow the physician to see and interact directly with the patient in real time.

Recent awards of nearly $190,000 from multiple organizations will allow the Trager Institute to support the expansion of additional resources, including:

• Telehealth and teletherapy for residents in long-term care facilities
• Training of staff and students to offer virtual interdisciplinary care coordination and chronic disease management
• Caregiver resources such as training, support groups and counseling services focused on Jefferson County and surrounding rural counties 
• Specialized mental health services for older adults to reduce social isolation and depression (PEARLS program)
• A state-wide virtual-friendly visitor program that provides patients, families, caregivers and nursing home residents and staff with resources to reduce social isolation

The funding is provided by the Geriatric Workforce Enhancement Program CARES Act, the National Family Caregiver Program Title IIIE (Administration on Aging) the Health Promotion and Disease Prevention Title IIIE (Administration on Aging) as well as others throughout Kentucky. These grants have created statewide partnerships and expanded the footprint of the institute and of the university.

“Given the expansion of social isolation in our community, our team has prioritized the dissemination of technology to community-dwelling older adults,” Faul said. “In addition to the currently funded efforts, we are looking forward to the possibility of additional funds that will allow us to provide iPads and Bluetooth technology to vulnerable community-dwelling older adults in Jefferson County and several rural counties, to establish a mini-virtual health clinic network across multiple Appalachian counties and to disseminate innovative contact tracing efforts through app-based, wearable devices and AI-based services.” 

The Trager Institute hosts weekly COVID-19 information sessions that focus on the experiences of older adults, caregivers and people with chronic conditions during the pandemic. The Aug.4 information session will explore the broader efforts of our community to address social isolation through technology innovation. This session will feature Wright, associate dean for rural health innovation in the UofL School of Medicine, and Rebecca Brown Rice, director of operations at the Louisville Healthcare CEO Council. This session will explore the innovative ways technology is used to reduce social isolation and loneliness both during and after the COVID-19 pandemic. As part of this conversation, the speakers will explore the latest developments in technology, such as SmartGlasses, and creative ways to re-imagine existing technology.

The virtual session will be held Tuesday, Aug. 4, at 10 a.m., at https://zoom.us/j/884298617.

If you or someone you know is experiencing social isolation or loneliness, contact the care team at the Republic Bank Foundation Optimal Aging Clinic at the UofL Trager Institute for assistance. The care team can be reached at 502-588-4340, Option 1, Option 1, or at tragerinstitute@louisville.edu. Additional resources are available at Community Action Kentucky Partnership and Area Agencies on Aging and Independent Living, which provide social interaction programs as well as other essential services such as in-home care and food delivery programs. 

You may be confident in your potential to pursue a career in biomedical research when the National Institutes of Health funds your work before you receive your Ph.D.

Two doctoral students in the University of Louisville Department of Anatomical Sciences and Neurobiology, Zach Whiddon and Kyle Whyland, have received funding from the NIH to support their research projects. The highly competitive F31 predoctoral training awards help set the researchers on a path to a career in research, requiring the same rigorous application process that seasoned investigators must go through to obtain NIH funding for their research.

“The receipt of an F31 award is an excellent credential and is an important part of building a career in science,” said Robin Krimm, Ph.D., a professor of anatomy and neurobiology and Whiddon’s mentor. “The award of an F31 also enable the student to be become more independent; their salary is paid from their own grant and they are responsible for reporting their research progress to the NIH.”

Whiddon, who moved to Louisville to pursue his Ph.D. after completing his master’s degree in cell and molecular biology at Eastern Michigan University, is working in Krimm’s lab to capture images of nerve cells within taste buds using a specialized technique Aaron McGee, Ph.D., another faculty member in the department, brought to UofL.

Neurons send long projections from the base of brain to the taste buds on the tongue, where terminal arbors, or branches, undergo rapid structural change. Using the technique McGee introduced, two-photon laser scanning microscopy, Whiddon developed a method to capture high resolution images of the branches as they connect to taste buds in live animal models and to document how those branches change over days and weeks.

“Taste bud cells have a very short life span, maybe 10 days. How do these neurons connect with replacement taste cells? To answer that we needed to be able to watch the neurons over time,” Whiddon said. “No one in the taste field has even attempted to look at the neurons over time. They did not think it was possible – until now.”

Already the research is showing that structural change happens much more rapidly than previously thought.

“We saw that in just a 12-hour period the arbors can add or subtract new branch ends, as much as 10 microns in length, which is very quick in terms of neural plasticity,” Whiddon said.

He plans to continue this field of research after he completes his Ph.D.

“Not a lot of people are doing this work, which is what makes it so exciting,” Whiddon said. “I think this research will be a good basis for a career – to adapt it and answer more questions. I’m interested in the plasticity aspect and what is controlling the structural rearrangements.”

Whyland’s research is focused on describing poorly understood brain circuits related to vision. The Jeffersonville, Ind., native earned a bachelor’s degree from Indiana University, majoring in psychology. Now working toward his Ph.D. with Professor Martha Bickford, Ph.D., Whyland is investigating how two specific parts of the brain, the superior colliculus and the parabigeminal nucleus, work together to process visual information and to control motor reflexes and defensive behaviors such as freezing or fleeing.

“We are trying to reverse engineer a little piece of wiring in the brain to give a model for how that might work in similar areas of the brain,” Whyland said.

Whyland’s research also takes advantage of specialized techniques being used in the labs at UofL.

“During the completion of his project, Kyle will receive training in a variety of neuroanatomical techniques, in vitro physiology and a technique called optogenetics in which specific brain cells can be activated with light pulses to interrogate brain circuit function,” Bickford said.

Both Whyland and Whiddon are grateful for the funding provided by the NIH – about $32,000 per year each – as well as the opportunity to learn the ropes of funding applications.

“If Kyle and Zach continue as research-active faculty members, they will be applying for grants throughout their careers,” Bickford said. “The F31 application gives students their first in-depth exposure to the NIH application process, including stringent reviews by a panel of experts.”

As with any competitive process, success is validating. For Whyland, however, the opportunity to revise and resubmit a project that initially was rejected was one of the most rewarding aspects of the experience.

“The first time I submitted it, it wasn’t even scored. By addressing the NIH reviewers’ specific concerns, I was able to resubmit it and get it funded,” Whyland said. “It was very satisfying to know that if you don’t get discouraged and try to address the criticisms, you can be rewarded. It was really motivating.”

 PhD student Kyle Whyland

Mengwei Jiang, a pharmacology and toxicology program PhD candidate in the laboratory of Dr. Wenke Feng, has been awarded a Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31) from the NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM for his PhD research entitled “Probiotic and intestinal miR194 regulation of bile acid metabolism in alcoholic liver disease”. This three year fellowship will support Mengwei’s research in the field of alcoholic liver disease.

Mengwei matriculated into the PhD program in pharmacology & toxicology via the PhD partnership program with Jilin University.

On Monday August 10 the Department of Microbiology & Immunology will host a virtual orientation for our Fall 2020 incoming students.  Faculty who are accepting new students into their laboratories will e-present their programs.  Welcome Taylor Garrison, Michelle Hallenbeck, Katelyn Sheneman, Peter Shin, Shikha Srivastava and Cassie Woolley!

Results from the second phase of the University of Louisville’s groundbreaking project to track COVID-19 in Jefferson County show that 4 to 6 times more people than previously reported may have been exposed to the virus since the beginning of the pandemic.

From June 10-19, researchers conducting Phase II of the Co-Immunity Project tested members of the Louisville community for both the presence of the novel coronavirus in the participant’s nasal passages and for antibodies against the virus in their blood. Samples were collected at five community drive-up locations across Louisville by UofL Health and researchers from the University of Louisville’s Christina Lee Brown Envirome Institute. Samples were analyzed by UofL’s Center for Predictive Medicine for Biodefense and Emerging Infectious Disease (CPM) in its Regional Biocontainment Laboratory (RBL).

To obtain a representative sample for the study, households in Jefferson County were organized into geographic regions based on U.S. Census Bureau tract boundaries. Households within each region were sent invitations to participate in proportion to the population of that region. Within the regions, areas that had higher concentrations of non-White residents were sampled at a higher rate to increase their representation.

Invitations were mailed to a total of 18,232 addresses. Based on the ages and sexes of all adults in the household as provided by those responding to the invitation, one adult from each household was asked to provide a sample.

The researchers tested 509 people who responded to the mailed invitations. An additional 1,728 community members booked appointments on their own and were tested after hearing about the study in the news or on social media. Many individuals who were invited to participate did not book an appointment. 

Of the 2,237 individuals who were tested, 10 percent were non-White. The ages of tested individuals was as follows:

• 21 percent between 18-34
• 40 percent between 35-59
• 40 percent age 60 or older

Residential locations of the 2,237 participants are shown in Map 1.  Overall, nearly 0.4 percent of the population of Jefferson County was sampled.

Analysis of the study data found that at least 0.05 percent of the participants had an active infection during the time of the study and approximately 4 percent (5.1 to 3.2 percent) of people had detectable levels of antibodies in their blood, indicating they had been exposed to the virus earlier in the year.

“These results allow us, for the first time, to more accurately estimate the spread of coronavirus within our community. If we extrapolate the results from this study to the general population, it would suggest that as many as 20,000 people may have been exposed to the virus – many more than the 3,813 cases reported in the city by the end of June,” said Aruni Bhatnagar, Ph.D., director of the Brown Envirome Institute.

This difference may be due to the fact that people did not have symptoms and were not aware they were infected.

“We were told by several participants that they believed they had COVID-19 before testing was widely available. Nonetheless, our preliminary data suggest that the estimated number of people who have had COVID-19 may be 4-6 times higher than those who have tested positive to-date,” said Rachel Keith, Ph.D., assistant professor of environmental medicine at UofL who conducted the study. “This suggests that the virus is much more widespread in our community than previously estimated. I believe this indicates a need for continued and widespread testing, including antibody testing, which plays an important role in understanding the spread of disease.”

“The random sampling of the population also allows us to calculate the true mortality associated with COVID-19,” Bhatnagar said. “Previous estimates of COVID-19-related mortality have varied from 0.5 to 15 percent. However, given that the city had reported 209 deaths by the end of June, our results suggest that the rate of mortality associated with the virus, at least in Kentucky, may be 1.3 percent. This is significantly higher than the 0.65 percent rate suggested by the CDC. Our research suggests that many who are infected with the virus nationwide have not been tested and that there is urgent need to continue random testing so that we can calculate the most accurate mortality rate,” Bhatnagar said.

The study data also provide an estimate of the spread of the infection in Louisville.

“Because participants were drawn from all parts of the city, we could estimate which areas have had the highest rates of infection,” Keith said. “Although we are still analyzing all our data, our early results show that the highest cluster of individuals exposed to the virus is in Western Louisville. (See Map 2).  We found that the prevalence of exposure was twice as high in non-White participants as in White participants. Most (54 percent) of those who tested positive for the antibody were between the ages of 35-59 years old,” she said.

The researchers cautioned that because so little is known about SARS-CoV-2 and because the rates of community infection and exposure are changing rapidly, the results of this survey are applicable only to the period of June 10-19.

“Although many individuals had detectable levels, the amount of antibodies in blood varied greatly among the participants,” said Kenneth Palmer, Ph.D., director of the CPM. “As a result, we are not sure to what extent they are protected from re-infection. Indeed, some of our early results show that the levels of antibodies decline rapidly within a month. Therefore, we are planning to re-measure individuals who had antibodies in their blood to see if those levels are maintained over time and if so, for how long.”

Currently, the researchers are repeating the antibody test in those health care workers who were found to have anti-SARS-CoV-2 antibodies during Phase I of the Co-Immunity Project. They also plan to repeat community-wide testing in Jefferson County in September.

This study was supported in part by the James Graham Brown Foundation. The Co-Immunity Project is a collaboration of the UofL Christina Lee Brown Envirome Institute, the Louisville Healthcare CEO Council and three health systems in Louisville – Baptist Health, Norton Healthcare and UofL Health.

A University of Louisville-born invention that may help treat cancer now has a commercial partner.

Qualigen Therapeutics Inc., a California biotechnology company focused on developing novel therapeutics for the treatment of cancer and infectious diseases, has signed a license agreement for the technology and plans to fund continued development with UofL to ready it for market.

The technology works by targeting the RAS protein, which sends signals that regulate when and where the body produces and grows new cells. When mutated, the protein turns into a “stuck accelerator pedal,” according to UofL researcher Geoffrey Clark, Ph.D., who co-invented the technology with colleagues John Trent, Ph.D., and Joe Burlison, Ph.D.

“Normally, it gets pressed when you need to grow and then the foot comes off and the cell slows down,” said Clark, professor of pharmacology and toxicology at UofL. “When it becomes mutated, the accelerator’s jammed on, with cells continuing to grow and ultimately becoming a cancerous tumor.”

The drug targets only the active RAS protein and, so far, has little toxic effect on healthy cells. Many current non-targeted treatments, such as chemotherapy, can hurt both healthy and cancerous cells, leading to painful side effects. By some estimates, targeting this mutation could stop the growth of at least a third of human tumors.

“The patient impact could be extremely broad because RAS is involved in a lot of different cancers,” Trent said. “It’s one of the holy grails that there has been limited success in targeting.”

Trent leads the Molecular Modeling Facility (MMF) at UofL Health – James Graham Brown Cancer Center and the UofL partnership with Dataseam, a non-profit with a network of school computers across the state. When the computers aren’t being used by students, they’re connected to act as a distributed supercomputer, allowing researchers to process and analyze huge amounts of data.

Trent used that capability to run through millions of cancer-fighting drug possibilities in a matter of days. The result was a drug that could inhibit the deregulated RAS protein. Development of the technology was supported by the UofL NIH REACH ExCITE program.

Qualigen holds an exclusive license to the technology through the UofL Commercialization EPI-Center, which works with startups and industry to commercialize university-owned technologies. This license agreement builds on a sponsored research agreement with Qualigen for the development of several small-molecule RAS Inhibitor drug candidates. Qualigen also has licensed and is developing other UofL technologies for fighting COVID-19 and cancer.

“Partnering on this new cancer-fighting technology is another example of the relationship we’ve developed with the University of Louisville,” said Michael Poirier, CEO of Qualigen. “We look forward to working with UofL and to advancing this important clinical program with the goal of developing an effective treatment for this unmet need."

If you are interested in supporting this cancer research at UofL, visit give.louisville.edu/JGBCC-Enhancement or contact Elea Fox at elea.fox@louisville.edu.