NIH – UofL News Thu, 16 Apr 2026 19:59:09 +0000 en-US hourly 1 Christina Lee Brown Envirome Institute awarded $11 million in new grants /section/science-and-tech/christina-lee-brown-envirome-institute-awarded-11-million-in-new-grants/ Fri, 06 Sep 2024 20:31:04 +0000 /?p=61273 Researchers in the have secured $11.27 million in new grants from the National Institutes of Health and the Department of Defense to fund projects related to cardiovascular health. The new funding will support work related to aging, peripheral artery disease, the impact of greening on health and Gulf War Illness.

  • $2.4 million from the National Institute on Aging will support work by Bradford Hill to investigate how aging leads to reduced blood flow to the heart in older individuals. Hill will study these changes and how this dysfunction could be prevented or corrected. The work may lead to opportunities to prevent age-dependent decline in exercise capacity and promote healthy aging.
  • $3.4 million from the National Heart Blood and Lung Institute was awarded for a clinical trial to test whether treatment with the nutritional supplement carnosine improves symptoms and progression in peripheral artery disease in which narrowing of arteries reduces blood flow to arms or legs. Aruni Bhatnagar, Shahid Baba and Amit Dwivedi will conduct the trial.
  • $4.67 million from the National Institute of Environmental Health Sciences will support the Green Heart Louisville Project, which studies how an increase in the number of trees and shrubs affects heart health. The team, led by Bhatnagar, recently reported results from their work that began in 2018 in South Louisville. The new award will allow the team to continue to gather data on community health for the next five years as the planted trees continue to grow.
  • $ 0.8 million from the Department of Defense was awarded to Daniel Conklin for a two-year project to investigate the role of inhaled agents in Gulf War Illness (GWI), a chronic condition affecting 25-32% of Gulf War veterans. GWI involves chronic pain, muscle fatigue, cognitive impairment, migraines and stroke. Conklin will investigate whether inhalation of volatile organic compounds and particulate matter from burning oil wells, burn pits, contaminated sand and chemical and biological weapons may have led to repeated local and systemic inflammation, causing the condition.

This most recent funding adds to the $11.6 in grants awarded to institute researchers announced earlier this year.

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UofL researchers are unmasking an old foe’s tricks to thwart new diseases /section/science-and-tech/uofl-researchers-are-unmasking-an-old-foes-tricks-to-thwart-new-diseases/ Mon, 27 Nov 2023 18:33:10 +0000 /?p=59614 When the body encounters bacteria, viruses or harmful substances, its innate immune cells, neutrophils, assemble at the site to combat the invader.

Bacteria and viruses have ways to avoid these defenses, however. Yersinia pestis, the bacteria that causes bubonic and pneumonic plague, for example, can hide from the immune system, allowing it to replicate in the body unhindered until it can overwhelm the host. This ability allowed Y. pestis to spread bubonic plague across Europe in the 14th Century, killing a third of the European population.

While plague may not be a serious threat to human health in modern times, researchers at the University of Louisville are studying Y. pestis to better understand its ability to evade the immune system and apply that understanding to control other pathogens.

“If you look at human plague, people don’t show symptoms right away even though they have an active infection because the bacteria is hiding from the immune system. Then all of a sudden there is a lot of bacteria, the immune system is overwhelmed and in the case of pneumonic plague, the individual dies from pneumonia,” said , professor in the UofL Department of Microbiology and Immunology.

Confocal microscopy images taken in the Lawrenz lab of neutrophils (blue) and Yersinia pestis (red).
Confocal microscopy images taken in the Lawrenz lab of neutrophils (blue) and Yersinia pestis (red). UofL photo.

Neutrophils are the immune system’s first responders, sending out protein molecules to summon other neutrophils to attack and destroy the invader. Among the first molecules sent out by neutrophils to signal an infection are Leukotriene B4 (LTB4) lipid molecules. Y. pestis interferes with the immune response by suppressing the LTB4 signals. Lawrenz has received a new $2.9 million, four-year grant from the National Institutes of Health to investigate how Y. pestis blocks LTB4. Ultimately, he expects this understanding will lead to ways to prevent Y. pestis from blocking the signals and hopefully, apply that understanding to other types of infections.

“This historic pathogen is really good at manipulating the immune system, so we use it as a tool to better understand how white blood cells like neutrophils and macrophages respond to bacterial infection,” Lawrenz said. “In this project, we are using Yersinia to better understand why LTB4 is so important to controlling plague. This understanding would apply to almost any infection of the lungs or other areas, and it probably could apply to viruses also.”

A member of the, Lawrenz has been studying plague bacteria for nearly two decades. His previous work includes discoveries of how Y. pestis acquires iron and zinc to overcome a host’s defense mechanism known as nutritional immunity and has increased understanding of how Y. pestis to hide from the immune system.

Katelyn Sheneman, a doctoral student in Lawrenz’s lab, also has received a prestigious $100,000 research award for trainees from the NIH. This grant will fund her research to understand how Y. pestis changes the contents of extracellular vesicles, cellular containers produced by immune cells that contain proteins, lipids such as LTB4 and other components. These vesicles are released into the bloodstream to communicate to other cells what is happening in their part of the body, such as an infection.

“My project is looking at how Y. pestis alters the number of vesicles being produced, what is being packaged in them and how other cells are responding to them,” Sheneman said. “We have some good evidence that pestis is able to manipulate the production of these vesicles, so we are going to look at the role the vesicles play in pulmonary infection and how that influence contributes to overall systemic infection.”

Since there is no effective vaccine against infection by Y. pestis and it has the potential to be used as a bioweapon, Lawrenz and Sheneman study Y. pestis in UofL’s Biosafety Level 3 facilities at the Regional Biocontainment Laboratory, part of a network of 12 regional and 2 national biocontainment laboratories for studying infectious agents. Biosafety Level 3 facilities are built to exacting federal safety and security standards in order to protect researchers and the public from exposure to the pathogens being investigated.

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UofL, partners awarded $12 million to advance biomedical innovation and entrepreneurship /section/science-and-tech/uofl-partners-awarded-12m-to-advance-biomedical-innovation-and-entrepreneurship/ Tue, 10 Oct 2023 11:00:25 +0000 /?p=59411 The University of Louisville and partners have been awarded $12 million to launch a new hub aimed at accelerating real-world impact of biomedical innovations through education, mentorship and financial support for aspiring entrepreneurs.

The Mid-South , backed by a four-year grant from the National Institutes of Health, spans a four-state network of Kentucky, Mississippi, Tennessee and Virginia. The hub is led by Vanderbilt University, with UofL leading efforts in Kentucky to transform academic discoveries into real-world products that advance human health and catalyze a medical innovation economy.

“UofL is a top-tier, Carnegie Research-1 university, and we are proud of our strong track record as a driver of health innovation and entrepreneurship,” said Kevin Gardner, executive vice president for . “We are excited to expand that work with the Mid-South Hub, joining our partner institutions to accelerate technologies and companies that can save and improve lives, creating opportunity here and throughout our region.”

NIH’s REACH program focuses on bringing basic science discoveries to market by providing entrepreneurial training for innovators on how to bring technologies to market; feedback from federal and industry experts; funding to support early-stage product definition studies; and project management support

UofL’s role in the new hub follows years of state leadership, since launching Kentucky’s first REACH program in 2015. The REACH efforts began at UofL and expanded statewide in 2019 through collaboration with KY Innovation, University of Kentucky and Kentucky Commercialization Ventures. Over nearly a decade, Kentucky REACH programs have coached more than 400 innovative faculty, staff and students across Kentucky public institutions and funded 45 technologies, leading to 18 new products and 11 patents filed.

“UofL has provided consistent leadership in driving these innovations from lab to market across the Commonwealth,” said Jessica Sharon, director of innovation programs and lead for the UofL Hub program. “Through this new Hub, we are very excited to work with our regional partner universities to train more innovator teams, helping them learn the product development process and lens.”

REACH is part of UofL’s unique suite of prestigious, grant-backed programs aimed at supporting the translation of research into viable commercial products. UofL is one of only a handful of universities in the country to host each of these innovation-associated programs — and it’s the only one to receiveallof them.

With the new Mid-South REACH Hub, UofL will expand on this programming by leveraging already strong partnerships with regional institutions. Last year, UofL partnered with Vanderbilt on a $15 million effort backed by the National Science Foundation to launch a new regional hub aimed at accelerating product innovation, entrepreneurship and economic development. The resulting NSF Mid-SouthInnovation Corps(I-Corps) Hub, one of only 10 across the U.S., is part of the operational backbone of the NSF’s , which helps translate academic research for the marketplace while expanding access and inclusion.

“Diverse perspectives are essential to turn university ideas into lifesaving tools in the hands of doctors,” said Vanderbilt lead, Robert Webster. “So many students and faculty share this vision—to their very core—but lack the business, legal and practical insights they need to get started…We know what it feels like and what it takes, and we can’t wait to help others unlock the potential of their ideas–and themselves–as innovators and entrepreneurs.”

NIH will contribute $4 million toward the Hub over four years, with more than $8 million in additional matching funds from partnering universities, state economic development entities and public-private partnerships.Kentucky matching funds are supported by the state Cabinet for Economic Development’s KY Innovation, UofL and UK. In addition to Vanderbilt and UofL, the other partner institutions are, Jackson State University, George Mason University and UK.

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Taming a frenzied immune system /section/science-and-tech/taming-a-frenzied-immune-system-uofl-receives-6-1-million-to-research-immune-response-discovered-during-the-pandemic/ Fri, 02 Jun 2023 17:39:18 +0000 /?p=58652 Researchers at the University of Louisville have received $5.8 million in two grants from the National Institutes of Health to expand their work to better understand and prevent immune system dysregulation responsible for acute respiratory distress, the condition responsible for serious illness and death in some COVID-19 patients. A separate $306,000 NIH Small Business Innovation Research grant supports early testing of a compound developed at UofL as a potential treatment.

During the pandemic, health care providers worked tirelessly to treat patients who became seriously ill with COVID-19. Some of those patients developed severe lung disease known as acute respiratory distress syndrome (ARDS) due to an excessive response of the immune system often called cytokine storm.

As they treated these critically ill patients, physicians and other providers at UofL Health shared their clinical insights and patient samples with researchers at UofL to discover the cause of the immune system overresponse.

“At one time we had over 100 patients with COVID in the hospital. Once they were on a ventilator, mortality was about 50%. We were looking at this issue to see why some people would do well while some developed bad lung disease and did not do well or died,” said Jiapeng Huang, anesthesiologist with UofL Health and professor and vice chair of the Department of Anesthesiology and Perioperative Medicine in the UofL School of Medicine.

The UofL researchers, led by immunologist Jun Yan, discovered that a specific type of immune cells, low-density inflammatory neutrophils, became highly elevated in some COVID-19 patients whose condition became very severe. This elevation signaled a clinical crisis point and increased likelihood of death within a few days due to lung inflammation, blood clotting and stroke. Their findings were published in 2021 in .

With the new NIH funding, Yan is leading research to build on this discovery with deeper understanding of what causes a patient’s immune system to respond to an infection in this way and develop methods to predict, prevent or control the response.

“Through this fruitful collaboration, we now have acquired NIH funding for basic and translational studies and even progress toward commercialization of a potential therapy,” Yan said. “That’s why we do this research – eventually we want to benefit the patients.”

Yan, chief of the UofL Division of Immunotherapy in the Department of Surgery, a professor of microbiology and immunology and a senior member of the Brown Cancer Center, will lead the new research, along with Huang and Silvia M. Uriarte, university scholar and professor in the Department of Oral Immunology and Infectious Diseases in the UofL School of Dentistry.

“COVID-19 continues to spotlight the impactful synergy between the clinical and research teams at the University of Louisville,” said Jason Smith, UofL Health chief medical officer. “Innovation is in the DNA of academic medicine. We collaborate to provide each patient the best options for prevention and treatment today, while developing the even better options for tomorrow.”

In addition to two research grants of $2.9 million each awarded directly to UofL, a $306,000 grant to a startup company will support early testing of a compound developed in the lab of UofL Professor of Medicine Kenneth McLeish that shows promise in preventing the dangerous cytokine storm while allowing the neutrophils to retain their ability to kill harmful bacteria and viruses. The compound, DGN-23, will be tested by UofL and Degranin Therapeutics, a startup operated by McLeish, Yan, Huang, Uriarte and Madhavi Rane, associate professor in the Department of Medicine.

“This is one more example of how UofL has led the charge in finding new and innovative ways to detect, contain and fight COVID-19 and other potential public health threats,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “This team’s new research and technology could help keep people healthy and safe here and beyond.”

The knowledge gained through these studies may benefit not only COVID-19 patients, but those with other conditions in which immune dysregulation can occur, such as other types of viral and bacterial pneumonia and autoimmune diseases, and patients undergoing cancer immunotherapy and organ transplantation.

The grants

Grant 1 – $2.9 million, four-year grant to UofL. Investigators will study the new subset of neutrophils Yan identified to better understand how they contribute to acute respiratory distress and clotting. They also will determine whether a novel compound will prevent these complications. They will use lab techniques and studies with animal models that allow for manipulation of certain conditions that cannot be done in human subjects.

Grant 2 – $2.9 million, five-year grant to UofL. This work examines a more comprehensive landscape to characterize different subsets of neutrophils and measure their changes over the course of COVID-19 disease progression and how neutrophils contribute to immune dysfunction.

Grant 3 – $306,000, one-year grant to Degranin Therapeutics and UofL for early testing of DGN-23, a compound developed at UofL, to determine its effectiveness in preventing or reducing immune dysregulation.

This research is supported by the National Heart, Lung, And Blood Institute under award numbers R01HL158779 and R43HL169129 and the National Institute of Allergy and Infectious Diseases under award number R01AI172873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

 

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UofL researcher receives $2 million to find ways to reduce effects of high-fat diet on the liver /post/uofltoday/uofl-researcher-receives-2-million-to-find-ways-to-reduce-effects-of-high-fat-diet-on-the-liver/ Tue, 02 Aug 2022 15:41:27 +0000 /?p=56942 It is estimated that about one in four individuals worldwide have nonalcoholic fatty liver disease (NAFLD), in which fat builds up in the liver. NAFLD can advance to inflammation and damage in the liver, a condition known as nonalcoholic steatohepatitis or NASH.

University of Louisville researcher Zhong-bin Deng has received a new grant from the National Institutes of Health to investigate how a high-fat diet contributes to these conditions and identify processes that may reduce liver inflammation and lead to new treatments.

Deng’s previous research revealed mechanisms in which dietary fat causes changes in the structure of epithelial cells, which comprise the lining of the walls of the intestines. When gaps form between these cells, toxins are allowed to move directly from the gut to the liver, where they cause an immune response and inflammation.

Building on this work, Deng, assistant professor in the Division of Immunotherapy within the Department of Surgery in the UofL School of Medicine, has been awarded $2 million from the NIH over five years to further investigate how these toxins cause the immune response in the liver, as well as test interventions that may reduce it.

“We are looking at how a high fat diet affects epithelial cells, allowing toxins to escape the gut and travel to the liver, leading to an immune response by macrophages in the liver and inflammation,” Deng said. “Also, we are trying to find a new therapy that could modulate the gut environment to control fatty liver disease.”

Deng’s research seeks to further understand the mechanism that leads to the gaps in the epithelial cells, which allow toxins produced by bacteria in the gut to move to the liver via the portal vein, known as the gut-liver axis. Deng and his team believe that the toxins cause the immune response of inflammation by changing Kupffer cells, white blood cells that reside in the liver. That inflammation can lead to liver cell damage.

“We propose that gut microbiota or the gut epithelial cells produce a signal that affects the Kupffer cells, causing inflammation in the high fat condition and may damage hepatocytes,” Deng said.

As part of the project, the researchers also will test whether an oligosaccharide found in human breast milk can be used to regulate the gut environment and mitigate the impact of the high fat diet on liver inflammation.

“We are trying to find out how to regulate this macrophage condition from an inflammation condition to an anti-inflammation condition,” Deng said.

“Dr. Deng’s new research evaluates highly novel aspects of nutrition in NAFLD,” said Craig McClain, professor and associate vice president for health affairs/research at UofL.

Jun Yan, director of the Division of Immunotherapy, said the research may lead to increased understanding of the causes of liver cancer.

“The research findings from this grant may also help understand how this type of liver inflammation leads to hepatocellular carcinoma, which causes approximately 30,000 deaths annually in the U.S.,” Yan said.

Results from Deng’s previous research in 2021.

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UofL researchers advocate clinical trials for CBD in COVID-19 treatment /section/science-and-tech/uofl-researchers-advocate-clinical-trials-for-cbd-in-covid-19-treatment/ Mon, 24 Jan 2022 19:24:15 +0000 /?p=55517 An interdisciplinary team of researchers from several institutions headed by the University of Chicago and including the University of Louisville has found evidence that cannabidiol (CBD), a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in mice.

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

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

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

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

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

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

For more detail on how medical-grade CBD shows promise as a treatment for COVID-19, check out the full story here.

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UofL receives $11.3 million from NIH for liver research center /section/science-and-tech/uofl-receives-11-3-million-from-nih-for-liver-research-center/ Mon, 21 Jun 2021 14:48:52 +0000 http://www.uoflnews.com/?p=53793 The University of Louisville Hepatobiology and Toxicology Center of Biomedical Research Excellence (COBRE) has received $11.3 million in funding from the National Institutes of Health to support its research into liver-related illness for an additional five years.

The UofL Hepatobiology and Toxicology Center was created in 2016 with an $11.5 million grant from the NIH to support unique research focused on liver injury and disease and toxicology. The center supports leading-edge research conducted by junior investigators with mentorship from senior researchers, as well as pilot projects and core laboratory facilities that support research across the university. The researchers’ goal is reducing the impact of many types of liver illness through prevention and the development of therapies.

Kentucky leads the nation in increases in cirrhosis-related deaths and in liver cancer-related deaths. According to research published in , mortality due to cirrhosis has been increasing in the U.S. since 2009, with the greatest increase in deaths from cirrhosis in Kentucky. Non-alcoholic fatty liver diseases affect approximately 25% of adults and 10% of children in the U.S.

“This vital research at the University of Louisville advances the health of Kentuckians and people throughout the world,” said UofL President Neeli Bendapudi. “Through this center, UofL researchers will continue to expand their work to find ways to prevent and treat liver illnesses, many of which today have no FDA-approved treatment.”

Researchers at the focus on liver injury, nutrition and gut-liver interactions as well as interactions between the liver and environment, toxicants and drugs. Their ultimate goal is to contribute to the prevention and treatment of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (a major cause of cirrhosis of the liver), alcoholic liver disease and liver cancer.

“This incredible cohort of researchers is discovering new ways to address the liver illnesses that afflict so many Kentuckians. I am thrilled that young researchers will continue to be supported with COBRE funding at UofL,” said Toni Ganzel, dean of the UofL School of Medicine.

In its first five years, four of the funded junior investigators in the UofL H&T Center received independent NIH research funding, making way for a new cohort of project researchers. The renewal of COBRE funding encourages a continuous supply of researchers in specialized areas of medicine and the search for new disease treatments.

“This unique thematic center is focused on liver injury, disease and toxicology. We evaluate critical barriers in our understanding of the development and progression of liver disease and we define potential therapeutic targets that could transform current practice,” said Craig McClain, associate vice president for health affairs and translational research and principal investigator for the UofL H&T Center. “This new phase will build on that success and extend and strengthen the scope of the program.”

COBRE project investigator Joshua L. Hood, M.D., Ph.D., left, and research technician Gina Bardi
COBRE project investigator Joshua L. Hood, M.D., Ph.D., left, and research technician Gina Bardi

“To push past the limitations of existing therapeutics, you need COBRE infrastructure grants to establish cutting-edge biomedical research centers and capabilities,” said Joshua L. Hood, a project investigator in the UofL H&T Center. “The more of these capabilities we have, the more we can explore multidisciplinary frontiers in biomedical science to facilitate the development of new treatments for liver-related cancer and other diseases.”

Current projects supported by the center include:

  • Yan Li, associate professor in the Department of Surgery, is investigating preventive strategies and possible mechanisms behind non-alcoholic steatohepatitis, a potential precursor of liver cancer.
  • Joshua L. Hood, assistant professor in the Department of Pharmacology & Toxicology, is examining how very small membrane-bound compartments known as nanovesicles that are released by cancer cells influence immune function in liver cancer.
  • Ming Song,assistant professor in the Department of Medicine, is studying the role of fructose consumption on the disruption of intestinal barrier function in non-alcoholic fatty liver disease.
  • Smita Ghare, instructor in the Department of Medicine, is investigating how alcohol-induced changes in the liver contribute to liver inflammation and injury.

UofL has a legacy of liver research dating to the 1970s when faculty members began investigating a cluster of cases of hepatic angiosarcoma, a rare liver cancer caused by exposure to vinyl chloride in a polymer manufacturing facility in an area of West Louisville known as Rubbertown. UofL researchers worked with the community and industry to document and reduce the effects of toxicants on worker health. UofL still maintains a biorepository of blood and liver tissue specimens begun during that research that serves as a resource for investigators studying the effects of environmental exposures on the liver.

In addition to research, the center provides support for community health. During the epidemic of Hepatitis A and C in the last decade, center investigators helped create the Kentucky Hepatitis Academic Mentorship Program. This program helped to train more than 140 primary care providers in the diagnosis and treatment of Hepatitis C. Those diseases now are declining.

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NIH funds UofL doctoral students’ work on taste buds and brain circuitry /post/uofltoday/nih-funds-uofl-doctoral-students-work-on-taste-buds-and-brain-circuitry/ Tue, 04 Aug 2020 14:27:24 +0000 http://www.uoflnews.com/?p=50907 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 PhD.

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, a professor of anatomy and neurobiology and Whiddon’s mentor. “The award of an F31 also enables 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 PhD 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, 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 PhD.

“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, Indiana-native earned a bachelor’s degree from Indiana University, majoring in psychology. Now working toward his PhD with Professor Martha Bickford, 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.

PhD student Kyle Whyland
PhD student Kyle Whyland

“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.”

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UofL receives $3.8M to test new gene therapy for heart attacks /section/science-and-tech/uofl-receives-3-8m-to-test-new-gene-therapy-for-heart-attacks/ Thu, 28 May 2020 15:09:20 +0000 http://www.uoflnews.com/?p=50464 When someone has a heart attack, it causes muscle cells in their heart to die, and the heart cannot regenerate these cells. Researchers at the University of Louisville have begun preclinical testing of a new gene therapy that stimulates regeneration of heart muscle cells.

The project, led by Tamer M.A. Mohamed, assistant professor of medicine in the UofL Division of Cardiovascular Medicine and the UofL Institute of Molecular Cardiology, has received a five-year, $3.8 million grant from the National Heart, Lung and Blood Institute.

“After a patient suffers a heart attack, the heart loses muscle cells, reducing the heart’s ability to pump blood to the rest of the body. Muscle cells in the heart do not regenerate on their own, leaving the heart permanently impaired,” Mohamed said. “We are developing a transient gene therapy approach to regenerate these muscle cells to heal the heart.”

The therapy involves transient overexpression of a combination of four cell-cycle regulating proteins to induce cell division in the heart muscle. The four cell-cycle regulators, cyclin-dependent kinase 1 (CDK1), CDK4, cyclin B1, and cyclin D1, are known collectively as 4F, or four factors. In , the process stimulated cell division in cardiomyocytes, or heart cells, leading to improved heart function.

The new study will determine further the effectiveness and safety of the therapy in animal models as well as in human heart segments using of a developed at UofL by Mohamed that keeps slices of human hearts alive for a longer period of time. The system mimics the environment of a living organ through continuous electrical stimulation and oxygenation, maintaining viability and functionality of the heart segments for six days, allowing more extensive testing. The for use by researchers outside UofL.

In addition to further testing the therapy’s effectiveness, Mohamed and other investigators will focus on approaches for the process that do not lead to tumor development in other cells.

“The challenge comes in avoiding development of cancer in other areas of the body, which appears to be a side effect of the process as seen in mice,” Mohamed said.

If it is successful, the work will lead to the start of in-human clinical trials.

 

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UofL receives groundbreaking new grant to spark commercialization of health research innovations /post/uofltoday/uofl-receives-groundbreaking-new-grant-to-spark-commercialization-of-health-research-innovations/ Mon, 04 Nov 2019 16:53:36 +0000 http://www.uoflnews.com/?p=48760 An elite $4 million grant received by the University of Louisville, the University of Kentucky, Commonwealth Commercialization Center (C3) and the Kentucky Cabinet for Economic Development demonstrates the power of partnership while paving the way to bring dozens of new med-tech and health-related companies to life across the state in the coming years.

The four-year Research Evaluation and Commercialization Hub (REACH) grant from the National Institutes of Health will help fund a public-private consortium, the Kentucky Network for Innovation & Commercialization – KYNETIC. The new organization will use NIH funding to advance the most promising biomedical research innovations from the state’s eight public universities and the Kentucky Community & Technical College System. Ultimately, its goal is to create startups that commercialize the technologies for public benefit.

KYNETIC, whose founding members will contribute a $2.56 million direct-cost match, will provide guidance and technical resources to advance the technologies toward commercialization. Additionally, KYNETIC will assist in scaling the resulting startups to help tackle some of the biggest health challenges facing the US population, such as cardiovascular disease, diabetes and cancer.

Innovations that KYNETIC will help bring to market may be new pharmaceuticals, therapies, devices and other health-related technologies. Those products could directly intervene in disease processes and conditions individuals suffer, or they may address health disparities like lack of health care access in rural areas or populations suffering disproportionate rates of disease and premature death.

As resulting startups move into clinical trials phases, many will rely on the strength of Kentucky’s public hospitals and health care systems.

UofL President Neeli Bendapudi said the expanding resources available through UofL Health will further support health care research.

“With the acquisition of Jewish Hospital and other KentuckyOne Health properties, researchers at UofL will have additional opportunities to recruit patients for clinical studies to advance research emerging from KYNETIC,” Bendapudi said. “Projects developed through KYNETIC will have the potential to further existing UofL research efforts in optimal aging, improve access to quality health care in underserved urban and rural regions, and bolster efforts to both attract and retain top faculty and students at UofL.”

In addition to its statewide approach, KYNETIC will intentionally seek both innovations and entrepreneurs from diverse and underrepresented groups.

Paula Bates, PhD, professor of medicine at UofL and co-principal investigator on the grant, said the state will benefit from broader collaborations facilitated by KYNETIC.

“When you get people from different backgrounds working together, you see innovation blossom,” Bates said. “I am looking forward to seeing some new collaborations, being able to share what we have learned and learn from other people in Kentucky. I think this is a really powerful way to reach everybody in Kentucky and get some great knowledge transferred and some great new ideas.”

Linda Dwoskin, PhD, UK professor of pharmaceutical sciences and co-principal investigator on the grant, said KYNETIC will benefit researchers, institutions and communities across Kentucky including underserved communities and populations.

“It is an honor to work with the University of Louisville, C3 and public academic institutions across the state to advance and accelerate innovative ideas that could lead to new products and technologies,” Dwoskin said. “Throughout the state we have untapped resources of inventive and entrepreneurial individuals and groups whom we hope to provide opportunities that will aid in transforming ideas and discoveries to tangible health benefits.”

“Kentucky’s ability to win this grant — one of only a handful ever awarded nationwide — was made possible in large part because of the unprecedented collaboration between our economic development cabinet, public universities and technical colleges in creating our non-profit commercialization center, C3,” said Governor Matt Bevin. “This grant further validates the significance of C3’s public-private structure and our decision to revitalize Kentucky’s innovation and entrepreneurial support system. Together, we can have a truly positive impact on the health of Kentuckians and people around the world.”

KYNETIC will leverage commercialization resources led by co-investigators Allen Morris, PhD, executive director of the UofL Commercialization EPI-Center, Ian McClure, executive director of the UK Office of Technology Commercialization, and April Turley director of C3’s Commercialization Core. It also will build on the experience brought by a current REACH hub at UofL () and other existing tech-transfer programs at UofL, as well as the regional IDeA biomedical technology transfer accelerator hub at UK

Check out more in the video below:

 

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