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Dunbar CAR T-Cell Program to bring more advanced immunotherapy treatment to cancer patients

Dunbar CAR T-Cell Program to bring more advanced immunotherapy treatment to cancer patients

Tom Dunbar with his son, Evan

Cancer patients in Louisville, in Kentucky and throughout the region soon will have access to some of the most advanced immunotherapy treatments available. Louisville resident Thomas E. Dunbar has pledged $1 million to the University of Louisville to create a specialized center to provide chimeric antigen receptor positive T (CAR T) cell therapies to patients at the UofL James Graham Brown Cancer Center and other centers in Kentucky and the Midwest. The new program will be named the Dunbar CAR T-Cell Program.

“This gift will allow both kids and adults to be treated right here in Kentucky with the most innovative cell-based immunotherapy being developed,” said Jason Chesney, M.D., Ph.D., director of the UofL Brown Cancer Center.

See a video of the announcement here.

In CAR T-cell therapies, immune cells are extracted from the patient’s own blood and then are genetically modified to fight cancer. The modified cells are infused back into the patient where they fight the cancer and create long-term immunity to its recurrence. In addition to dramatic treatment results, CAR T-cell immunotherapy leads to fewer toxic side effects than traditional chemotherapy.

“Patients who have been treated with all the conventional therapies who then underwent treatment in clinical trials with CAR T cells had dramatic response rates. Eighty-three percent of kids in the original trial who had lethal, terminal B-cell acute lymphoblastic leukemia responded to this therapy,” Chesney said.

CAR T-cell therapy is FDA approved for treating patients who have B-cell acute lymphoblastic leukemia, who are mostly children, as well as adults who have an adult form of a B-cell (non-Hodgkin’s) lymphoma. This technology also is being tested for treatment of other cancers through clinical trials. Until now however, these treatments have been available primarily in larger coastal cities outside of the Midwestern United States.

“At the UofL Brown Cancer Center, we feel strongly that these advanced therapies should be available not just to people in New York or California or Texas, but to people in Kentucky, Indiana, Tennessee and Illinois. If you live in these areas, it is going to be very hard for you to be treated a thousand miles away with a therapy like this,” Chesney said. “And any patient with health assistance through Medicaid is likely to be covered only if the treatment is delivered within the state.”

The Dunbar CAR T-Cell Program will include laboratories for manufacturing the CAR T cells and will administer both FDA-approved and clinical-trial therapies to adult and pediatric cancer patients. The program intends to expand clinical trials and clinical research using CAR T-cell therapy to treat additional cancer types in Louisville. The goal is for the facilities to be fully functional and receiving patients by Sept. 30, 2020.

Tom Dunbar’s son, Evan, lost his battle to cancer with neuroblastoma in 2001 at the age of 6. In 2009, Wally Dunbar, Tom Dunbar’s father, lost his battle with melanoma. This year, Tom’s physician wife, Stephanie Altobellis, M.D., helped identify his own cancer.

“Kentucky is at ground zero, with the nation’s highest rates of cancer diagnosis and death,” Tom Dunbar said. “It’s completely unacceptable. We have to lead the charge right here where the need is the greatest and we can do the most good. We need treatments that are not toxic. Watching our loved ones miserable with pain, often just from the treatments, and yet still die in front of us simply can’t be the best that we can do.”

How CAR T cells work

T cells are key immune cells in the body that attack cancer cells. CAR T cells are T cells that have been isolated from the patient’s blood and then genetically modified to more effectively destroy the cancer cells.

A non-infectious virus is used to insert genes into the T cells that express a receptor specific to proteins, or antigens, present on cells of the cancer to be treated. The armed, loaded T cell is drawn into close proximity to the cancer cell, and the new cell sends a signal for the T cell to kill the cancer cell.

“We add the receptor gene into the T cells, which makes them stick to the cancer cells like Velcro,” Chesney said. “In theory, all cancers have unique antigens on their surface that we can target with this approach. We are nudging the immune system on to really hit the target, in this case the cancer cells.”

The sophisticated technology requires the use of a specialized clean room for genetically manipulating the patients’ immune cells. The clean rooms, known as Good Manufacturing Practice (GMP) laboratories, require specialized documentation and equipment to protect the individuals working there and ensure a sterile and controlled environment for the cells.

The Dunbar CAR T-Cell Program will include two GMP laboratories, one for use in pediatric therapies to be named for Evan Dunbar and one for adult therapies to be named for Altobellis. These labs are intended to support not only clinical trials and patient treatment at the UofL Brown Cancer Center, but also in other health centers in Louisville, Lexington and elsewhere.

“Our goal for the Dunbar CAR T-Cell Program GMP labs is to be a hub manufacturing facility for CAR T cells, not just in Kentucky, not just in the region, but for the entire country,” Chesney said.

For Dunbar, the goal is to improve cancer treatment for patients.

“The burden is on each of us to create a better future for our children,” Dunbar said. “Working together, we can ensure Louisville is equipped to provide the durable cures, free of side-effects, that we desperately need.”

HSC Research Forum October 29th

CTRB 101/102 from 12 pm - 1 pm.

Topics include: NIH Updates, Sponsored Programs Administration Realignment, KBRIN, Proteomics Core Facility, JHFE Research Enhancement Grants, and more!

UofL research warns millennials of hepatitis C

UofL research warns millennials of hepatitis C

John Myers, Ph.D.

Hepatitis C virus (HCV) infection has skipped a generation and become a predominantly millennial disease, according to research by John Myers, Ph.D., UofL Professor of Pediatrics. 

Myers and his team screened 82,243 individuals for HCV infection in 2016-2018 in Norton Healthcare in order to assess trends in a large health care system in an area with a high prevalence of opioid use and HCV infection. The investigators defined millennials as individuals born between 1980 and 1995, and baby boomers were those born between 1945 and 1965.

Traditionally, baby boomers were the largest drivers of HCV, though millennials have been shown in previous research to be the fastest-growing population of those infected with the virus. However, those studies were performed at single institutions with small sample sizes.

Millennials who were HCV-positive increased by 53 percent over the study period while the population of HCV-positive individuals among baby boomers decreased by 32 percent.

“The opioid crisis has led to a drastic demographic shift, and currently the typical HCV-infected individual is a younger male. Without interventions, this trend will continue for upwards of seven years, plateauing near the demarcation of millennials and generation Z.” Myers said.

The data were presented Oct. 3 in Washington at IDWeek, the combined medical meeting of four adult and pediatric infectious disease societies. 

 

 

 

 

 

 

Professor John Wise Sr. receives education award from Environmental Mutagenesis and Genomics Society

John Wise Sr

 

 

Dr. John Wise Sr., Professor of Pharmacology and Toxicology recently received the EMGS Education Award from the Environmental Mutagenesis and Genomics Society.  The award is bestowed in recognition of sincere dedication to student and young investigator members of the Environmental Mutagenesis and Genomics Society.

Pharmacology & Toxicology PhD candidates receive awards

Two Pharmacology and Toxicology PhD candidates recently received awards. 

Both are supported by T32 predoctoral fellowships on the NIEHS T32 UofL Environmental Health Sciences Training grant.

Jam ie Young received an award to honor her excellent oral presentation at the 13th Conference of International Society for Trace Element Research in Human (ISTERH) at Bali, Indonesia, September 22 – 26, 2019.  Jamie is pursuing her PhD in the laboratory of Professor Lu Cai.




Christine  Kim received a full travel award to attend the 16th Annual APA Environmental Health Scholars Retreat, November 1-3, 2019, in Providence, RI. During the retreat the focus will be on helping you continue to acquire the tools needed to be effective in the field of pediatric environmental health.  Christine is pursuing her PhD in the laboratory of Professor Brian Ceresa.



M&I Ph.D student receives University ExCITE grant

Henry NabetaM& I student Henry Nabeta received an ExCITE award of $50,000 for his project "Developing Q-Griffithsin as a new anti fungal agent".  UofL’s ExCITE program is funded through the National Institute of Health’s Research Evaluation and Commercialization Hub (REACH) program. The goal of the program is to support proof-of-concept centers (hubs) that facilitate and accelerate the translation of biomedical innovations into commercial products that improve patient care and enhance health.

UofL's Clayton Smith named Best Doctor by LEO Weekly

UofL's Clayton Smith named Best Doctor by LEO Weekly

Clayton M. Smith, M.D.

Clayton M. Smith, M.D., associate professor of medicine in the UofL School of Medicine and internal medicine physician with UofL Physicians, has received 1st place, Best Doctor in LEO Weekly’s Readers’ Choice Awards, winning over more than 100 nominees. Smith focuses his clinical practice on primary care internal medicine and LGBTQ health. He will be honored Oct. 3 at the Readers’ Choice Awards Party. 

See the LEO Readers Choice Awards list here.

NCI Cancer Education Program participants receive awards at Research!Louisville

NCI Cancer Education Program participants received best research poster awards at Research!Louisville held September 13, 2019:

Norbert J. Burzynski Award Professional Student Category

 

1st place:  Ankur Patel 

ZEB mRNA Expression is Affected by Long Non-coding RNA ZFAS1

Mentor: Susan Galandiuk

 

2nd place:  James Burton 

Effect of Long Non-Coding RNA ZFAS1 on Epithelial-To-Mesenchymal Transition Protein Expression in Colorectal Cancer Cell Lines 

Mentor:  Susan Galandiuk

 

3rd place: Daniel Hodge 

The effects of arylamine N-acetyltransferase 1 on tumor immune response

Mentor: David Hein

 

Norbert J. Burzynski Award Undergraduate Student Category


1st place:  Grace Lian

Investigating molecules that confer sensitivity to AS1411 in lung adenocarcinoma cells

Mentor: Paula Bates

 

2nd place:  Kate Tarvestad

Low-Level Chronic Arsenic Exposure and its Effect on the ErbB Family Receptor Tyrosine Kinases.

Mentor:  Brian Ceresa

 

3rd place:  Destine Ede 

A Potential Novel Treatment for Neurofibromatosis Type 1 via RAS Inhibition 

Mentor: Geoffrey Clark

 

Pharmacology and Toxicology graduate students receive awards at Research!Louisville

Department of Pharmacology and Toxicology graduate students received awards for best research poster presentations at Research!Louisville on September 13, 2019.  

Master’s Basic Science Graduate Student Awards

 1st place:  Jeffrey Warner

“Soluble epoxide hydrolase inhibition: a novel therapeutic strategy in alcoholic liver disease”  

Mentor: Irina Kirpich

 

2nd place:  Sean Raph

“KVß2 mediates vasodilation in response to redox changes of the NADH:NAD+ ratio.”

Mentor: Matthew Nystoriak.

 

2nd place:  Angeliki Lykoudi 

“Overexpression of has-miR-186 induces anchorage-independent growth and chromosomal alterations in arsenic exposed human keratinocytes: A preliminary study”

Mentor: J. Christopher States

 

Doctoral Basic Science Graduate Student Awards

3rd place:  Adrienne Bushau-Sprinkle 

“Mechanistic insight for increased susceptibility to cisplatin nephrotoxicity with NHERF1 loss”. 

Mentor: Eleanor Lederer

 

"Write Winning Grant Proposals" Seminar

Seminar sponsored by the Kentucky Pediatric IDeA Grant Research Center (K-PIRC).

Wednesday, January 22, 2020, 8:30am - 4:30pm, HSC location TBD. Seminar is free, but registration is required: https://www.eventbrite.com/e/write-winning-grant-proposals-tickets-71511421587. Registration will close Friday, January 3rd. For more info contact Jackie Boyd at 502.588.0774 or

DOM members make impressive showing at 2019 Research!Louisville

Annual event held at the University of Louisville highlights, promotes excellence and public awareness of health sciences research at the Louisville Medical Center
DOM members make impressive showing at 2019 Research!Louisville

Ming Song, Ph.D., of the UofL Division of Gastroenterology, Hepatology & Nutirtion accepts his 1st place award in the Faculty Award in Basic Science category at the recent 2019 Research!Louisville

VIEW A PHOTO GALLERY FROM 2019 Research!Louisville

It's become a tradition for members and affiliates of the University of Louisville Department of Medicine to make an impact at the annual Research!Louisville competition at UofL, and 2019 was no exception.

Celebrating its 24th year, Research!Louisville is an annual celebration of health-related research aimed at promoting excellence and public awareness in health sciences research in Louisville while also generating additional funding for health sciences research.

A panel of university faculty judges selected the winners of this year's contest from hundreds of entries in the categories of professional/clinical students, basic science grad students, postgraduates and faculty.

"The research performed by members of the Department of Medicine is second to none," Dr. Eleanor Lederer, interim chair of the UofL Department of Medicine said. "Research!Louisville gives our Department the opportunity to showcase the important investigative work we do every day."

Here's a look at finished at or near the top in their respective categories:

Master’s Basic Science Graduate Student Award

  • 2nd place: Sean Raph - "KVß2 mediates vasodilation in response to redox changes of the NADH:NAD+ ratio"
    Mentor: Matthew Nystoriak
  • 1st place: Jeffrey Warner - "Soluble epoxide hydrolase inhibition: a novel therapeutic strategy in alcoholic liver disease"
    Mentor: Irina Kirpich

Doctoral Basic Science Graduate Student Award

  • 3rd place: Adrienne Bashau-Sprinkle - "Mechanistic insight for increased susceptibility to cisplatin nephrotoxicity with NHERF1 loss"
    Mentor: Eleanor Lederer

Engineering Student Award

  • 3rd place: Alexa Melvin - "A 3D Printed Microfluidic Manifold to Prepare Plasma from Whole Blood"
    Mentor: Nichola Garbett

Postdoctoral Fellow Award

  • 2nd place: Josiah Hardesty - "Genetic ablation of Fpr2 in mice increased susceptibility to alcohol-mediated liver injury due to enhanced inflammation and impaired antimicrobial defense"
    Mentor: Irina Kirpich
  • 1st place: Banrida Wahlang - "Hepatic injury caused by the environmental toxicant vinyl chloride is sex-dependent"
    Mentor: Matthew Cave

Faculty Award in Basic Science

  • Winner: Ming Song - "Dietary Fructose Induces Intestinal Oxygenation Likely Contributing to Gut Microbiota Dysbiosis"

Ruth Greenberg Award for Excellence in Medical Education Research

  • 3rd place: Barbara Head - "Does faculty training and development improve skills and competencies that lead to interprofessional educational programs in palliative care? he iPEX Program"

Louisville Chapter-Women in Medicine and Science

  • 3rd place: Lilibeth Lanceta - "Oncolytic Virotherapy for the treatment of ER+ palbociclib-resistant breast cancer"
    Mentor: Yoannis Imbert-Fernandez
  • 2nd place: Smita Ghare - "Tributyrin attenuates alcohol-induced chemokine up-regulation via epigenetic mechanisms - Relevance to hepatic inflammation and Injury in ALD"
    Mentor: Shirish Barve

Prodigy Award for High School Translational Research

  • 2nd Place: Maxwell Martin - "Automation of DNA-ligand MD simulations with free energy calculations for enrichment of high affinity ligands in virtual screening"
    Mentor: John Trent

NCI Cancer Education Program Norbert J. Burzynski Award Undergraduate Student Category

  • 1st place: Grace Lian - "Investigating molecules that confer sensitivity to AS1411 in lung adenocarcinoma cells"
    Mentor: Paula Bates

30 Pharmacology & Toxicology graduate students presenting their research posters at Research!Louisville

30 Pharmacology & Toxicology graduate students are presenting their research posters at Research!Louisville Tuesday morning September 10 from 9-am to noon in the Kosair Charities Clinical and Translational Research Building.

Over 40 NCI Cancer Education Program participants will present their research posters at Research!Louisville

Over 40 NCI Cancer Education Program participants will present their research posters at Research!Louisville.  The posters are available here.

The NCI cancer education program selects professional and undergraduate students from the University of Louisville and other universities across the USA.  Further information is available at http://uofl.me/nci-r25.

UofL Liver Researchers included in "Best of the Liver Meeting" at AASLD Annual Meeting

Congratulations to our Liver Researchers—two of the many abstracts from our group that were submitted to and accepted for presentation at the annual meeting of the American Association for the Study of Liver Diseases have been chosen for inclusion in the “Best of the Liver Meeting” summary slide deck in the Alcohol-Related Liver Disease Category.  These are:  

1.  Keratin 18 is a Biomarker for the Diagnosis and Prognosis in Acute Alcoholic Hepatitis. (Vatsalya Vatsalya, Matthew C Cave, Maiying Kong, Leila Gobejishvili, Heather Clair, Cameron Falkner, John Craycroft, Mack C Mitchell, Gyongyi Szabo, Arthur J McCullough, Srinivasan Dasarathy, Svetlana Radaeva, Bruce Barton and Craig J McClain)

2.  Fpr2-/- Mice Are More Susceptible to Alcohol-Induced Liver Injury Due to Impaired Antimicrobial Defense. (Josiah E Hardesty, Jeffrey B Warner, Dennis R Warner, Ying Song, Craig J McClain, Irina A Kirpich).

Department Welcomes Incoming Students of 2019

Monday, August 12, the Department of Microbiology & Immunology welcomed  the incoming M&I graduate students with a luncheon in the CTRB.  Incoming students include Richard Bautista, Easton Ford, Kamille Rasche, Omar Sarker, Caleb Whitley and Matthew Woeste.

2019 New student orientation lunch.                

M&I PhD Candidate receives NIH F31 award

PriceSarah Price, a graduate student in the laboratory of Dr. Matthew Lawrenz, has been awarded a Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31) from the National Institute of Allergy and Infectious Diseases for her PhD research entitled “Identification of a novel zinc acquisition system in Yersinia pestis”. This three year fellowship will support Sarah’s research in the field of nutritional immunity.

 

                                     

Rare Disease Day (8/2/19)

August 2, 2019 was proclaimed as Rare Diseases Day in Kentucky.  Gov. Bevin made the proclamation at the University of Louisville.  He was accompanied by Dr. Thomas Abell, Director of GI Motility in the UofL School of Medicine.  Dr. Abell studies gastroparesis, a rare disease, and is considered to be a world authority on the condition.

16 UofL Department of Medicine faculty named 'Top Docs' for 2019

Annual survey conducted by Louisville Magazine and the Greater Louisville Medical Society leads to accolades for several UofL medicine faculty
16 UofL Department of Medicine faculty named 'Top Docs' for 2019

Louisville Magazine recently honored 16 faculty members from the UofL Department of Medicine as "Top Docs" for 2019

A group of 16 members of the University of Louisville Department of Medicine, the flagship department of the UofL School of Medicine, were recently recognized as "Top Docs" as voted on by their peers in the Louisville medical community in the August 2019 edition of Louisville Magazine.

"These results clearly demonstrate that the faculty of the University of Louisville Department of Medicine command the respect and regard of our community colleagues," Dr. Eleanor Lederer, interim chair of the UofL Department of Medicine said. "Our reputation as a resource for excellence in cutting edge clinical care is growing, and I am proud to serve as the interim chair of this dynamic department."

According to the guidelines of the survey, questionnaires were sent to the more than 2,000 members of the Greater Louisville Medical Society asking the question, "If you or a member of your family were in need of medical care or treatment, who among Louisville-area doctors would you choose to provide medical care in the following specialties?"

From the UofL Department of Medicine, those recognized include (categories as listed in the publication):

UofL Cancer Education Program Undergraduate Participants to Present Research Posters Friday Aug 2

The 19 undergraduate students in the 2019 cohort of the University of Louisville Cancer Education Program will present their research posters at the Undergraduate Research Symposium scheduled Friday, August 2 from noon to 3 pm in the Kosair Charities Clinical and Translational Research Building. 

In addition to UofL, undergraduate students in the 2019 cohort are pursuing their undergraduate studies at Emory University, Holmes Community College, Knox College, Oklahoma State University, Purdue University, University of Cincinnati, University of Dayton, University of Kentucky, University of North Carolina, University of Notre Dame, and the University of Southern California.  A listing of the 2019 cohort together with their faculty mentors is available here.

The student research posters to be presented on Aug 2 are available here.

Risks of vaping by children: What parents can do

As e-cigarette use increases among teenagers, it’s important for parents and caregivers to know the associated risks and what they can do to foster healthy habits in their children.

Although the liquid used in e-cigarettes does not include tobacco, it contains nicotine, which is highly addictive and poses dangers to children, said Heather Felton, M.D., medical director of the UofL Pediatrics – Sam Swope Kosair Charities Centre.

“Nicotine raises blood pressure and spikes adrenaline, thus increasing heart rate and the likelihood of having a heart attack,” Felton said. “It also can harm a child’s developing brain and parts of the brain that control attention, learning, mood and impulse control.”

The amount of nicotine in vaping liquids can vary among brands, but many contain more nicotine than a traditional cigarette. For instance, a single JUUL pod contains as much nicotine as a pack of 20 regular cigarettes, Felton said. The liquid can be a poison when swallowed or absorbed through skin or eyes. Also, vaping often leads to traditional tobacco product use.

What parents can do:

  • Set a good example by being tobacco-free.
  • Talk to your child about vaping and the risks of use.
  • Seek help from your child’s physician to explain to your child the health risks of vaping.
  • Encourage teachers and administrators at your child’s school to enforce tobacco-free policies.