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Bruce Keisling, executive director of the UTHSC Center on Developmental Disabilities (CDD), recently received a new $113,670.00 award from the Department of Health and Human Services. The grant is part of a $150 million federal investment by the Biden administration to expand the public health workforce within the Administration for Community Living's disability networks.
The UTHSC CDD is one of 67 University Centers for Excellence in Developmental Disabilities (UCEDDs) and 60 Leadership Education in Neurodevelopmental and related Disabilities (LEND) programs in the United States. These programs were established by the federal government to develop interdisciplinary training, clinical and community service, and applied research related to developmental disabilities.
The UTHSC center includes 10 disciplines, from speech and language pathology to social work and from psychology to developmental pediatrics. As UCEDD director, Dr. Keisling leads a wide array of faculty and staff working to meet the needs of people with disabilities in our community.
Dr. Keisling, a 2021 Fellow of the American Association on Intellectual and Developmental Disabilities, also holds the Shainberg Professorship in Developmental Pediatrics, and is an associate professor of Pediatrics at UTHSC.
Congrats to Dr. Kui Li, professor in the department of Microbiology, Immunology, and Biochemistry, and Dr. Lu Lu, professor in the department of Genetics, Genomics and Informatics for their newly funded collaborative grant!
Drs. Li and Lu are multiple PIs on a $423,500 award from the National Institute of Allergy and Infectious Diseases for their project, "Host genetic determinants regulating susceptibility/resistance to SARS-Co-V-2."
Their study is aimed at understanding the host genetic factors that affect the abilities of the SARS-CoV-2 virus to multiply and to inflict disease in infected hosts. Dr. Li and Dr. Lu hope to identify those critical nodes that help predict disease severity or are amenable to therapeutic and/or prophylactic targeting.
We're celebrating a new cross-college collaborative project that just snagged national funding!
The National Institute of Arthritis and Musculoskeletal and Skin Diseases has awarded $372,680 in support of the study, "Muscle GPRC6A regulation of protein turnover with overload and disuse recovery." James Carson, PhD, FACSM, senior associate dean for Research and Graduate Studies in the college of Health Professions, is the lead PI. Dr. Carson is also deputy director of the Tennessee Institute of Regenerative Medicine (TennIRM) and professor in the department of Physical Therapy.
Min Pi, PhD, associate professor in the division of Nephrology in the department of Medicine, also serves as a PI on the project. Other members on the team are Stephen Alway, PhD, FACSM, dean of the college of Health Professions, professor in the department of Physical Therapy and in the department of Physiology; and Darryl Quarles, MD, UTMG endowed professor, director of the division of Nephrology in the department of Medicine, and associate dean for Research in the College of Medicine.
The National Institute of Allergy and Infectious Diseases has awarded $2.4 million to Radhakrishna Rao, PhD, vice chair and professor in the Department of Physiology at the University of Tennessee Health Science Center, to develop medical countermeasures to treat gastrointestinal acute radiation syndrome. Radiation exposure due to large-scale nuclear incidents is a global concern. Gastrointestinal… Read More
The National Institute of Allergy and Infectious Diseases has awarded $2.4 million to Radhakrishna Rao, PhD, vice chair and professor in the Department of Physiology at the University of Tennessee Health Science Center, to develop medical countermeasures to treat gastrointestinal acute radiation syndrome.
Radiation exposure due to large-scale nuclear incidents is a global concern. Gastrointestinal acute radiation syndrome is associated with severe morbidity (nausea, vomiting, diarrhea, etc.) and high mortality. With no FDA-approved therapeutics for the syndrome, understanding how radiation causes tissue injury is a high priority in identifying targets to develop medical countermeasures.
The gut microbiome, consisting of trillions of microorganisms in the gastrointestinal tract, is involved in functions critical to health and well-being. Radiation alters gut microbiome composition and functions, leading to the development of gastrointestinal acute radiation syndrome. Dr. Rao’s goal is to identify intestinal radio-protective microbiota and understand how they prevent and mitigate radiation injury. His team aims to develop gut microbiome-targeted medical countermeasures to treat radiation injury.
“With our knowledge from nuclear disasters in Chernobyl in 1986 and Fukushima Daiichi in 2011, and the nuclear risk in the current Ukraine war, it is necessary to develop therapeutics to treat radiation injury,” Dr. Rao said. “We are excited about our finding from studies in animal models that feeding Lactobacillus species 24 hours after irradiation could mitigate gut injury, endotoxemia, and systemic inflammation.”
Collaborators on the project are Sue Chin Lee, PhD, assistant professor in the Department of Physiology; Francesco Giorgianni, PhD, in the Department of Pharmaceutical Sciences; Fridtjof Thomas, PhD, professor in the Department of Preventive Medicine; and Laurentia Nodit, MD, professor in the Department of Pathology.
During his 30 years at UTHSC, Hungarian-born Gábor Tigyi, MD, PhD, Harriet Van Vleet Endowment Professor and former chair of the Department of Physiology in the UTHSC College of Medicine, has traveled to his birth country many times. However, in December, the trip back was a milestone. He traveled to Budapest at the invitation of… Read More
During his 30 years at UTHSC, Hungarian-born Gábor Tigyi, MD, PhD, Harriet Van Vleet Endowment Professor and former chair of the Department of Physiology in the UTHSC College of Medicine, has traveled to his birth country many times. However, in December, the trip back was a milestone. He traveled to Budapest at the invitation of the NOVOFER Foundation for Technical and Intellectual Creation, a nonprofit dedicated to the recognition of scientific and technological discoveries, to receive one of the most prestigious awards of his career: the 2022 Dénes Gábor Prize for scientific innovation.
The award, named after the Nobel Prize winner Dénes Gábor, is given to a Hungarian scientist working abroad who is doing exceptional research with translational applications. Dr. Tigyi’s groundbreaking discoveries in lysophosphatidic acid (LPA) biology are nothing short of revolutionary and have launched an entirely new field of research that today is populated by fellow investigators around the world.
In 1986 at the University of California, Irvine, Dr. Tigyi discovered the lipid mediator LPA. Ten years later at UTHSC, he showed that LPA is able to protect the genetic integrity of intestinal stem cells after radiation exposure, allowing lifesaving tissue recovery. This work garnered him international attention, yielding several patents and a drug compound, Rx100, that is in the FDA approval process for treating radiation injury.
He’s referring to his realization, which came many years later, that LPA is an essential regulator of stem cell pluripotency. “It’s what keeps a stem cell a stem cell,” he said. “With the radiation countermeasure, we were working to help the stem cells survive that energy overload that comes from ionizing radiation. But we were basically working with stem cells and keeping them alive. After 20 years, I’ve come to realize that this LPA molecule is essential for maintaining stemness of stem cells. That’s the real thing.”
The ways in which this knowledge has been translated into treatments by his UTHSC group and international collaborators sounds like the stuff of science fiction. An example is his work with professors Il-Ho Jang, PhD, Department of Oral Biochemistry and Molecular Biology, and Eun-Jin Seo, Department of Physiology, both faculty at Pusan National University, South Korea, on a project to activate dormant stem cells in the root of the tooth.
“We discovered that if you block the LPA2 cell surface receptor on a stem cell, dental pulp stem cells will grow into odontoblasts, which form dentin the bony part of the tooth,” he said. “When you have a cavity, the bony part of the tooth erodes, exposing the dental pulp in the middle of the tooth. Your dentist solves this by drilling a hole in the tooth, removing the pulp, putting some resin then a cap on your tooth. It’s basically a dead piece of bone. We’ve developed a method where a dentist can instead use a little bit of a gel plug that has been soaked in an inhibitor of the LPA2 receptor, which makes the dental pulp stem cells differentiate into odontoblasts which regrow the tooth. No more filling! We heal the tooth by regeneration, not destruction.”
Another major project, a collaboration with the lab of Duane Miller, PhD, Professor Emeritus in the UTHSC Department of Pharmaceutical Sciences in the College of Pharmacy, is the development of inhibitory compounds that regulate LPA function in malignant cancer stem-like cells that can stop cancer growth and spread.
“We found the second most upregulated gene in cancer stem cells is the enzyme that makes LPA, and it has three fundamental effects: 1) it makes cancer stem cells resistant to radiation and chemotherapy, 2) it makes them spread and metastasize, and 3) it shuts downs the anti-tumor immunity.” Dr. Tigyi is the lead investigator, with Sue Chin Lee, PhD, associate professor in Physiology, as a principal investigator. Also on the team are Corinne Augelli-Szafran, PhD, vice president of Scientific Platforms at Southern Research in Birmingham, Alabama, and Raul Torres, PhD, professor of Immunology and Microbiology at the University of Colorado.
“It’s phenomenal. This has been in our hands such a long time and we didn’t realize,” Dr. Tigyi said, still excited by the discovery. “There’s so much more to do. I wish I were 20 years younger.”
Since his arrival at UTHSC in 1992, he has been continuously funded by multiple national grants, with the overall amount totaling nearly $70 million to his lab and startup companies. He was named Harriet Van Vleet Chair in Oncology Research in 2006, and associate vice chancellor for Research and Industry Relations in 2016.
Dr. Tigyi received his medical degree from the University Medical School of Pecs, Hungary, and holds a PhD in cellular and molecular neurobiology. His extensive postgraduate work was conducted in biochemistry at the University of Uppsala, Sweden, and at the Max-Planck Institute for Biophysical Chemistry, Gottingen, Germany, as well as the University of California, Irvine.
“I am forever grateful to my teachers. From kindergarten I can name them, all the way to my graduate mentor. They were extraordinary people who taught me a lot more than I realized when I was working with them. They are with me forever.”
He is just as quick to acknowledge his collaborators and co-workers. “The research is not just mine; it belongs in equal part to the people I work with. I’ve had extremely good luck with having good coworkers. I am standing on their shoulders.”
The Department of Defense has awarded $1.9 million to Jay H. Fowke, PhD, MPH, MS, chief of the Division of Epidemiology and professor in the Department of Preventive Medicine at the University of Tennessee Health Science Center (UTHSC), to study why Puerto Rican men have higher than expected prostate cancer mortality. Puerto Rican men have… Read More
The Department of Defense has awarded $1.9 million to Jay H. Fowke, PhD, MPH, MS, chief of the Division of Epidemiology and professor in the Department of Preventive Medicine at the University of Tennessee Health Science Center (UTHSC), to study why Puerto Rican men have higher than expected prostate cancer mortality.
Puerto Rican men have a higher prostate cancer mortality compared to non-Hispanic white or Hispanic men living in the United States. Prostate cancer mortality among Puerto Rican men is second only to black men in the U.S., but has remained largely unstudied. Most studies combine men from all Spanish-speaking regions into a single group, labeling them Hispanic or Latino, and ignore regional cultural, economic, and lifestyle differences that could impact prostate cancer prognosis. Diabetes is more prevalent in Puerto Rico than in any state or territory. While it is known that diabetes and obesity adversely affect prostate cancer prognosis, the role of diabetes specifically on prostate cancer mortality in Puerto Rico is unknown.
Dr. Fowke and his team will work to determine if diabetes interacts with obesity to increase aggressiveness of prostate cancer in Puerto Rican or black men. They will examine differences in how diabetes and obesity interact between Puerto Rican, non-Hispanic white, and black men, looking for mechanisms that might explain the unexpectedly high prostate cancer mortality in Puerto Rico. The team will compare the effects of diabetes and obesity on prostate cancer prognosis among Puerto Rican patients at the San Juan VA Medical Center to black and non-Hispanic white patients at the Durham VA Medical Center in North Carolina. The studies will involve comparing gene expression pathways in prostate tissue between diabetic prostate cancer patients in the three ethnic groups. This analysis will be the first genomic investigation of prostate cancer in Puerto Rico, and the first to investigate the diabetes impact on prostate tissue across these groups. The team’s findings can then be translated to personalized clinical interventions.
“With this study, we hope to produce results that can be used to develop clinical trials to test careful diabetes and obesity characterization, and personalized diabetes management with obesity to improve prostate cancer prognosis for Puerto Rican, black, and non-Hispanic white patients,” Dr. Fowke said.
The National Institute on Alcohol Abuse and Alcoholism has awarded $2.6 million to Alex M. Dopico, MD, PhD, Van Vleet Chair of Excellence and professor in the Department of Pharmacology, Addiction Science, and Toxicology (PHAST) at the University of Tennessee Health Science Center, to study cerebrovascular dysfunction that could contribute to alcohol-induced blackouts. Alcohol-induced blackouts… Read More
The National Institute on Alcohol Abuse and Alcoholism has awarded $2.6 million to Alex M. Dopico, MD, PhD, Van Vleet Chair of Excellence and professor in the Department of Pharmacology, Addiction Science, and Toxicology (PHAST) at the University of Tennessee Health Science Center, to study cerebrovascular dysfunction that could contribute to alcohol-induced blackouts.
Alcohol-induced blackouts are a form of amnesia caused when a person drinks heavily enough to temporarily block the transfer of memories from short- to long-term storage — known as memory consolidation — in the brain’s hippocampus. These blackouts can occur in anyone who heavily drinks within a short period, regardless of age, education, socioeconomic status, drinking history, sex, or sexual orientation. A serious consequence of alcohol misuse, alcohol-induced blackouts drastically increase the risk for dangerous behaviors, injuries, and other harms.
Previous studies have sought the cellular basis of alcohol-induced blackouts, focusing primarily on neuronal or glial elements. Dr. Dopico’s study departs from all previous research by focusing instead on blood perfusion of this brain region. His project builds on his years of research and his discovery of a molecular site in BK channel protein receptors where alcohol is recognized and interacts to make cerebral arteries contract.
Dr. Dopico’s team, including Anna Bukiya, PhD, and Brendan Tunstall, PhD, both faculty in the PHAST department, will explore how, at concentrations reached in the brain during alcohol-induced blackouts, these amino acids cause artery constriction, regional hippocampal ischemia, and ultimately, blackouts. The team will use a wide array of methodologies, from computational models of alcohol-BK receptor interaction to behavioral testing in animal models. They aim to fully characterize the vascular target for alcohol, the first step in designing drugs to counteract alcohol-induced blackouts. They will examine whether there is a difference between the biological sexes in how the target responds to alcohol action. Finally, they will test the effectiveness of their newly discovered vasomodulator as a possible treatment.
“As recently done in other fields within the neurosciences, such as neurodegeneration, cognition deficits, and dementia, we are bringing a vascular component(s) as central to the pathophysiology of substance use disorders, alcohol-induced blackouts in particular,” Dr. Dopico said.
Two new reports by researchers at the University of Tennessee Health Science Center provide the first published description of unplanned interruptions in radiation cancer treatment across a major U.S. city in the COVID-19 era, according to their authors. The studies placed special focus on how risk for radiotherapy interruption varied by patient race, socioeconomic status,… Read More
Two new reports by researchers at the University of Tennessee Health Science Center provide the first published description of unplanned interruptions in radiation cancer treatment across a major U.S. city in the COVID-19 era, according to their authors. The studies placed special focus on how risk for radiotherapy interruption varied by patient race, socioeconomic status, and home neighborhood.
According to the researchers, the initial article, published in the International Journal of Radiation Oncology – Biology – Physics, provides the first report of how interruption rates were impacted by the COVID-19 pandemic across a U.S. metropolitan region. The second, published in Advances in Radiation Oncology, studied interruptions in cancer radiation treatment associated with unplanned hospitalization during therapy. David Schwartz, MD, professor and chair of the Department of Radiation Oncology in the UTHSC College of Medicine, led the team that performed the work.
The COVID-19 manuscript documented a persistent 36% overall decline in patient volume across the first pandemic year. Although overall interruption rates trended slightly downward during the first pandemic year, financially disadvantaged populations undergoing longer planned courses of radiotherapy remained at risk for major gaps in treatment. Detailed geospatial analysis of Memphis added critical insights, revealing interruption risk concentrating within racial minority communities living in urban downtown neighborhoods. The authors noted their findings could be leveraged to design strategies to enhance access to treatment in specific communities well beyond the pandemic.
In the second article, Dr. Schwartz’s team reviewed five years of radiation treatment records at UTHSC to catalog associations between unplanned hospitalization events and radiotherapy interruption. The three most common causes for hospitalization were malnutrition/dehydration, respiratory distress/infection, and fever/sepsis. The team identified factors predictive for interruption coinciding with hospitalization, including African American race, Medicaid/uninsured status, and having lung or throat malignancies.
The team again leveraged geospatial mapping to find interruption events clustering among uninsured/Medicaid patients living in urban, low-income, majority African American neighborhoods. However, these events were not limited to poor neighborhoods. Patients from middle-income suburban communities were also impacted.
“Associations between hospitalization and treatment interruption were driven by location. Risk was observed in poorer urban neighborhoods and middle-income suburban locations alike, independent of patient race. Only the wealthiest residential areas enjoyed low interruption rates,” Dr. Schwartz said.
“Patients who have the greatest access to financial resources also frequently have access to interpersonal support and social resources to keep them out of the hospital during radiotherapy. The best way to make cancer care equitable is to bring relevant resources directly to patients that don’t benefit from that level of support.”David Schwartz, MD
Dr. Schwartz’s team is now actively working to make these resources available to all Memphis communities. He serves as one of the lead investigators of a multidisciplinary program at UTHSC focused on automated identification of patients at risk for treatment interruption, coupled with downstream community-based patient support tailored to individual patient needs.
Additional team members from UTHSC who co-authored this work included Elizabeth Gaudio; Adam Hubler, MD; Daniel V. Wakefield, MD, MPH; Lydia Makepeace, MD; Matt Carnell; Ankur M. Sharma, MD; Bo Jiang, MPH; Wesley B. Garner, MD, MPH; Drucilla Edmonston, MD; John G. Little; Michelle Y. Martin, PhD; Arash Shaban-Nejad, PhD; Nariman Ammar, PhD; Fatma Gunturkun, PhD; Robert Davis, MD, MPH; Cem Akkus, PhD, MPH; and Whitney Brakefield, MS.
Researchers from Tennessee Oncology, the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, the Bredesen Center for Data Science and Engineering at the University of Tennessee, Knoxville, the University of Alabama at Birmingham, the University of Oxford, Vanderbilt University Medical Center, and the University of Memphis were also involved in the studies.
Scientists led by the University of Tennessee Health Science Center (UTHSC) and the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland are exploring the elaborate interplay between genes, sex, growth, and age and how they influence variation in longevity. Their findings, which are being published in the peer-reviewed journal Science, are an important step in understanding why some people live… Read More
Scientists led by the University of Tennessee Health Science Center (UTHSC) and the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland are exploring the elaborate interplay between genes, sex, growth, and age and how they influence variation in longevity. Their findings, which are being published in the peer-reviewed journal Science, are an important step in understanding why some people live longer than others and provide a basis for future studies to improve healthspan.
Robert Williams, PhD, chair of the Department of Genetics and Genomics in UTHSC’s College of Medicine, along with Johan Auwerx, MD, PhD, professor and director of the Laboratory for Integrated and Systems Physiology at EPFL, started a program in 2016 to define genetic factors underlying aging and lifespan. “Finding common molecular pathways that control differences in rate of aging is critical to our understanding of how individuals differ in their health and lifespan,” Dr. Williams said. “Such insights may help us work out ways to intervene rationally.”
Drs. Williams and Auwerx worked with colleagues at the National Institute on Aging’s Interventions Testing Program (ITP), which donated DNA of over 12,000 mice to the project. ITP mice are genetically heterogeneous. Each of the 27,574 mice studied is a full sibling, sharing half its genetic inheritance with each other mouse in the program, and each has a known lifespan, making them an ideal system to study.
EPFL and UTHSC researchers measured the genetic makeup of more than 3,000 mice, all of them genetic brothers or sisters. The mice were then genotyped and allowed to live until their natural death. The researchers then explored the relationship between DNA difference and differences in the lifespan of each mouse. This genetic mapping allowed the teams to define stretches of DNA in genomes that affect longevity. The results show the DNA segments, or loci, associated with longevity are largely specific to sex, with females having a region in chromosome 3 that affects lifespan. When the males who died early due to non-aging-related reasons were removed from the analysis, additional genetic signals started to emerge, suggesting some genetic variations only affect lifespan after a certain age.
In addition to finding genetic determinants of longevity, the researchers explored other contributors. In general, bigger mice die younger. The researchers found that some, but not all, of the genetic effects on longevity are through effects on growth. One of the non-genetic effects may be how early access to food affects growth. They observed that mice from smaller litters tended to be heavier adults and live shorter lives. Mice from larger litters that had to share their mother’s milk with more siblings, grew more slowly and lived longer on average. The researchers corroborated these trends of early growth versus longevity in large human datasets with hundreds of thousands of participants.
Beyond characterizing how longevity is affected, the researchers worked to find genes most likely to play a role in longevity determination. They measured the effect of DNA variation on how genes are expressed and compared their analyses with multiple human and non-human databases. From this they nominated a few genes likely to modulate aging rates. They then tested the effects of manipulating these genes in roundworms and found that a subset of gene perturbations did in fact affect the lifespan. The results of this study will be a rich resource of aging genes that will hopefully guide the design of therapies that not only extend lifespan, but also healthspan.
Funding for the project was provided by the NIA, EPFL, the European Research Council, the Swiss National Science Foundation, and the Glenn Foundation for Medical Research. The paper, titled “Sex- and age-dependent genetics of longevity in a heterogeneous mouse population,” is in the October 2022 issue of Science.
Radhakrishna Rao, PhD, vice-chair and professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), has received two large national awards totaling $5 million for separate studies involving the gut as a therapeutic target for treating disease. Dr. Rao is known worldwide for his two decades of research into the… Read More
Radhakrishna Rao, PhD, vice-chair and professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), has received two large national awards totaling $5 million for separate studies involving the gut as a therapeutic target for treating disease. Dr. Rao is known worldwide for his two decades of research into the structure and regulation of the intestinal epithelium, which forms the gut barrier preventing allergens, toxins, and pathogens from entering the bloodstream.
This month, the National Institute of Allergy and Infectious Disease awarded Dr. Rao $2.5 million to study how acute radiation syndrome affects the gut microbiome and intestinal mucosal barrier function. Public exposure to radiation due to large-scale incidents is a rising global concern. The gastrointestinal tract is one of the first organs injured by radiation, but no FDA-approved treatments exist for gastrointestinal acute radiation syndrome.
Dr. Rao and his team will work to determine how radiation alters innate intestinal immunity by suppressing antibacterial peptide production in the gut. They also aim to identify how supplementing such peptides can prevent and treat radiation injury. This project will test and develop a new FDA-regulated drug that can be used in the event of radiation exposure to the public.
“I believe the gut is a critical target for treating many diseases, including acute radiation syndrome,” Dr. Rao said. “Therefore, it is exciting to have this unique opportunity to explore intestinal Paneth cell-based innate immunity as a novel therapeutic target for developing a treatment strategy to treat acute radiation syndrome.”
Earlier this year, the National Institute on Alcohol Abuse and Alcoholism awarded Dr. Rao $2.5 million for a project to identify therapeutic targets to develop drugs to treat alcohol-associated diseases. Dr. Rao and his collaborators have identified certain calcium channels (TRPV6 and CaV1.3) in the intestinal epithelium that drive alcohol-induced endotoxemia and systemic inflammation by enforcing intestinal epithelial junction disruption and mucosal barrier dysfunction. The project will test how the coordinated activities of those channels mediate an alcohol-induced rise in epithelial cellular calcium leading to gut permeability and systemic inflammation. It will also evaluate the potential of calcium channel blockers to mitigate and prevent alcohol-induced endotoxemia and liver damage.
“Once again, the intestine is the crucial therapeutic target for alcohol-associated liver disease,” Dr. Rao said. “I have no doubt that more evidence will emerge supporting the gut as the primary therapeutic target for many systemic diseases. Science is accomplished best by multidisciplinary approaches. I am fortunate to have a team of collaborators with expertise in diverse discipline.”
Dr. Rao is also a recent awardee of the Veterans Health Administration Merit Review Award to study the impact of chronic stress on alcohol-induced tissue injury at the gut-liver-brain axis.
The National Cancer Institute has awarded more than $5.2 million to a team lead by researchers from the University of Tennessee Health Science Center (UTHSC) for a study that will fill critical gaps in knowledge around obesity-mediated cancer risk. Liza Makowski, PhD, professor in the Division of Hematology and Oncology in the UTHSC College of… Read More
The National Cancer Institute has awarded more than $5.2 million to a team lead by researchers from the University of Tennessee Health Science Center (UTHSC) for a study that will fill critical gaps in knowledge around obesity-mediated cancer risk. Liza Makowski, PhD, professor in the Division of Hematology and Oncology in the UTHSC College of Medicine, is the lead investigator on the award.
Obesity has been linked to an increased risk of and a worse prognosis for several types of cancer. A number of related factors contribute to obesity’s pro-tumor effects, including suppression of the immune system (immunosuppression). The underlying mechanics that control how and to what extent obesity-mediated immunosuppression increases cancer risk remains an untapped niche in cancer research.
Dr. Makowski’s team hypothesizes that obesity changes the gut microbiome, which can impact the immune system’s ability to keep watch on the start of cancer, potentially through microbially-derived metabolites. In this project, the team will study patients undergoing bariatric surgery to follow metabolic and immune changes with weight loss over time. In a complementary study, healthy subjects who are lean or obese of varying age and races will be examined for certain biomarkers of risk. Advanced single cell sequencing and informatics will help define associations identifying patients at risk using machine learning. Pre-clinical studies will be conducted to identify the specific cell machinery in pre-cancerous microenvironments that have high impact on the start and progression of cancer. They will test these mechanisms to determine how microbially-modified metabolites may impact immune-cancer cell crosstalk.
This award bridges investigators across four additional universities working with UTHSC. The two other principal investigators are Joseph Pierre, PhD, assistant professor in the College of Agriculture and Life Science at the University of Wisconsin-Madison, and Jeffrey Rathmell, PhD, director of the Vanderbilt Center for Immunobiology and associate director of the Vanderbilt Institute of Infection, Immunology, and Inflammation. Colleagues from Wake Forest University School of Medicine and the University of Memphis College of Health Sciences are also integral collaborators on this project.
“We are excited to be one of five projects chosen by the NCI to examine obesity and cancer risk as part of the NCI’s Metabolic Dysregulation and Cancer Risk Program,” Dr. Makowski said. “The Mid-South has a diverse population with a large minority representation, high rates of obesity, and tragically poor patient cancer outcomes, which pose an opportunity for our exceptional transdisciplinary team to leverage impactful lifestyle changes or generate therapeutic strategies for interventions to decrease cancer risk. Outcomes from this study will define beneficial mediators of obesity-mediated cancer risk that will shed light on how to reduce the risk of cancer or improve treatments.”
Other UTHSC investigators on the team include bariatric surgeon Matthew Davis, MD, in the Department of Surgery; Francesco Giorgianni, PhD, in the Department of Pharmaceutical Sciences; and Robert Williams, PhD, Lu Lu, MD, and David Ashbrook, PhD, in the Department of Genetics, Genomics, and Informatics.
The National Institute of Deafness and Other Communication Disorders has awarded $1.9 million to John Boughter, PhD, professor in the Department of Anatomy and Neurobiology and co-director of the Neuroscience Institute at the University of Tennessee Health Science Center (UTHSC), to study the brain circuitry involved in processing novel tastes and foods. Max Fletcher, PhD,… Read More
The National Institute of Deafness and Other Communication Disorders has awarded $1.9 million to John Boughter, PhD, professor in the Department of Anatomy and Neurobiology and co-director of the Neuroscience Institute at the University of Tennessee Health Science Center (UTHSC), to study the brain circuitry involved in processing novel tastes and foods. Max Fletcher, PhD, associate professor in the Department of Anatomy and Neurobiology, is also a principal investigator on the award.
Neophobia, or the fear of anything new, is an important concern in pediatric psychology. In children, the term generally refers to a tendency to reject unknown or new foods. A persistent unwillingness to try new foods or break from routine food choices can have both acute health consequences for a child and long-lasting effects that lead to eating disorders, poor health outcomes, and disease.
Little is known about the underlying neural circuits involved in taste neophobia. In this project, Dr. Boughter, Dr. Fletcher and their team will work to understand how information regarding the newness or familiarity of tastes are encoded within brain circuits. They hypothesize that neophobia is driven by enhanced responses in both the cortex and thalamus, while the process of learning that a new stimulus is safe to consume is mediated by a neurotransmitter (acetylcholine) released from forebrain inputs. Findings from the study will increase understanding of taste learning and the mechanics within sensory regions that process new sensations.
“Food neophobia is an important behavior for most animals,” Dr. Boughter said. “It is important to understand its neural organization in order to gain new insights into how feeding behaviors are controlled by the brain.”