This Core, led by Robert Clark, MD, and Peter Hornsby, PhD, promotes the career development of early-stage geroscience investigators. Accessing the research education, training, and career development resources of UT Health San Antonio’s Institute for Integration of Medicine and Science (IIMS), as well as the robust and unique aging research resources and education programs in South Texas, our Mentored Research Career Development (San Antonio OAIC RL5) Scholars are trained in the operative mechanisms in the aging process, and in the design of pre-clinical and clinical interventions for diseases and conditions that affect older adults. The RL5 award mechanism is similar to the KL2/K12 award mechanism, but permits more flexibility in the percent effort required of the Scholar. All San Antonio OAIC RL5 Scholars will have research projects, mentoring teams, and defined short- and long-term career goals. The REC will also sponsor various training and mentoring research experiences. UT Health San Antonio and its partners offer a rich pool of available trainees and mentors, additional sources of career funding, laboratories, and multiple opportunities for didactic coursework. San Antonio OAIC RL5 scholars are fully eligible for pilot project support from the Pilot and Exploratory Studies Core (PESC).
We plan to support a cohort of one San Antonio OAIC RL5 Scholar annually for up to two years per award, contingent upon grant renewal. Leveraging the research education, training and career development resources of IIMS and the robust and unique aging research resources and research education programs in South Texas, the program enhances the clinical and translational research knowledge and experience of basic scientists, develop mechanistic research skills of clinical investigators, and facilitate collaborations among basic and clinical researchers.
San Antonio OAIC RL5 scholar applicants should be either junior faculty members or senior postdoctoral fellows transitioning to a full-time academic faculty appointment prior to the start of the award. Applicants will have a graduate or professional degree (e.g., MD, DDS, PhD, RN, MPH, PharmD) and must exhibit evidence of high motivation, a pro-active work style, strong academic achievement, and dedication to scholarship. Other eligibility requirements include:
- Should be able to commit 50 to 75% full-time professional effort (6-9 calendar months) to the program and its related clinical/translational science research activities.
- Applicants must not be, or have been, a Principal Investigator on an NIH R01 or R21 award, a Project Leader on a subproject of a Program Project (P01), Center (P50, P60, U54) or equivalent research grant award, or a Principal Investigator of a mentored research career development grant. Applicants may have received prior support on Institutional or Individual NRSA grants (F or T) or NIH Small Grant (R03).
- RL5 participants may receive salary support from other federal sources consistent with the institution’s salary scale, as long as those sources do not specifically prohibit such salary supplementation. Nevertheless, individuals supported by NIH training and career development mechanisms (K, T, or F awards) may not receive salary or stipend supplementation from the RL5 program.
- Note that dual employment by UT Health San Antonio and the VA may be restricted, depending upon the amount of VA effort. Federal salaries are not considered part of the suggested 50-75% RL5 Scholar institutional commitment.
Terms of the Award
- Salary support of 50-75%, subject to the NIH salary cap
- Award period of up to two years, with Year 2 support dependent on satisfactory progress in Year 1
- Scholarly travel support of $2,000
- Research project support of up to $20,000
Features of Training Experience
Program Entry: Scholars will be assessed individually to determine the competencies needed to move them forward to the next phase of their translational research career focused on aging and geroscience. Each Scholar will work with a primary mentor, along with a multidisciplinary mentoring team, based on the principle that optimal career development depends on working both with scientists making fundamental discoveries and with clinicians providing for the needs of older adults with multiple co-morbidities. Milestones for each scholar will be developed within the context of their research project and individual career objectives.
Program Progress: During the program, the multi-disciplinary Mentoring Team will monitor Scholar progress at quarterly meetings. Progress will be assessed and documented through written semi-annual self-evaluations with input from the mentors, along with the REC Directors.
Program Transition: Throughout the program there will be a focus on honing grant-seeking skills (e.g., individual career development awards), with activities including the K12 Seminar Series – Scholars Preparing Aims for R and K awards (SPARK) Peer-Mentoring Seminars and Scholars Optimizing Achievement in Research (SOAR) Seminars. As Scholars complete the program, each will be assisted with the next step of their career. In addition, these Phase 2 Scholars will meet annually with the REC Directors for follow-up on career development status.
- Scholars Preparing Aims for R and K awards (SPARK) Peer-Mentoring Seminars. This forum consists of interactive meetings among the RL5, KL2, and K12 Scholars and Directors, for the Scholars to describe their research progress and to receive advice and critical feedback on documents in preparation for grants or manuscripts. Draft proposals are critiqued, problems discussed, and suggestions made to resolve roadblocks that may occur and impede progress in research and career development. The SPARK Seminars require each Scholar to iteratively produce a career development award application (e.g., K01, K08, K23, VA CDA, foundation programs) or research grant application (e.g., R21, R01). These meetings are also designed to enhance the sense of community among diverse Scholars within the UT Health San Antonio, allowing the sharing of ideas and strategies across disciplines. This cross fertilization potentiates the development of new insights into each other’s work. The rotation schedule is set up such that each Scholar presents their work in progress every two to three months.
- Scholars Optimizing Achievement in Research (SOAR) Seminars. SOAR seminars are designed to facilitate the successful transition of Scholars into independent investigator status via a series of sessions pertaining to a wide range of issues involved in career development. These seminar topics are chosen by the Scholars to fit their needs and are facilitated by faculty and staff with expertise in the particular topic.
Core Activities: In addition to the IIMS/San Antonio OAIC RL5 Program curriculum, translational aging research-focused training opportunities include:
- Introduction to Translational Science – provides a broad perspective on translational science processes from basic science discovery to population implementation and policy research
- Clinical practicum with a San Antonio OAIC faculty member to learn principles of Geriatrics Assessment and measurement (especially important for individuals without prior geriatrics training)
- Pharmacotherapy of Special Populations – section related to older adults provides instruction on drug utilization, risks for adverse effects, drug-drug interactions, and clinical evaluation
2021-2023 San Antonio OAIC Scholars
Jamie Walker, MD, PhD,
Research Project: Establishing a San Antonio Longevity and Successful Aging Cohort
Dr. Walker is an Assistant Professor of Pathology, a board-certified neuropathologist, Co-Director of the Biggs Brain Bank and Co-Leader of the South Texas ADRC Neuropathology Core. Her research focuses on resistance to the development of Alzheimer’s disease (AD) pathology and resilience in the presence of AD pathology (pathology present, but no cognitive decline). It is important to study these resistant and resilient individuals because it will help us uncover mechanisms that could prevent or protect against AD pathology, which could lead to new therapies. With this RL5 project, our goal is to establish a successful aging cohort where we will recruit these resistant and resilient individuals and learn their secrets of healthy aging. We will be studying both the physical and cognitive aspects of aging and how these interact.
Juan Pablo Palavicini, PhD
Research Project: Effects of mTOR inhibition on central and peripheral ceramide metabolism in old marmosets and cognitively impaired human subjects
Dr. Palavicini has a broad background in biochemistry, neuroscience and metabolism, with more than 16 years of research experience. During his graduate studies at the Institute of Neurobiology of the University of Puerto Rico, Dr. Palavicini studied protein-RNA interactions within the central nervous system. Dr. Palavicini joined the field of neurodegenerative diseases in 2011, first through a postdoctoral appointment at the laboratory of Dr. Madepalli Lakshmana at the Torrey Pines Institute for Molecular Studies, Florida, where he studied the molecular mechanisms underlying the role of RanBP9 on Alzheimer’s disease (AD) using cell culture systems and transgenic mouse models. In 2013, Dr. Palavicini joined the laboratory of Dr. Xianlin Han as a postdoctoral fellow, where he studied the role of myelin lipids on the pathogenesis of AD, aging, and diabetes using multiple animal models. To this end, he received a Postdoctoral Fellowship from the American Diabetes Association (2015-2017).
In 2019, Dr. Palavicini was appointed Assistant Professor at UT Health SA’s Barshop Institute for Longevity and Aging Studies and Department of Medicine, Diabetes Division. Dr. Palavicini is currently pursuing an independent line of research focused on studying the role of ceramides, important signaling molecules that in excess become lipotoxic, in the context of aging and aging-related diseases, including AD and diabetes. In addition, Dr. Palavicini is developing a new line of research, in collaboration with Dr. Sarah Hopp, focused on studying the role of phospholipase C gamma 2 (PLCG2) in the context of Alzheimer’s disease and aging. Finally, Dr. Palavicini is currently participating in multiple lipidomic ancillary studies of ongoing Alzheimer’s, diabetes, and aging-related clinical trials.
Tiffany Cortes, MD
Research Project: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging in Older Overweight/Obese Adults with Insulin Resistance
Dr. Cortes is an Assistant Professor of Medicine in the Division of Endocrinology, and the Sam and Ann Barshop Institute for Longevity and Aging Studies at the UT Health San Antonio. She completed her medical training at UT Health San Antonio, her residency in Internal Medicine University of Texas Medical Branch and Endocrinology fellowship at Mayo Clinic. She is active in teaching, clinical care, and research. Dr. Cortes’ research focus is on understanding the relationship between type 2 diabetes and frailty in older adults, and interventions to address metabolic dysfunction in older adults. Her RL5 project aims to determine whether GLP1 receptor agonists can improve physical function and muscle mass in older adults with prediabetes or diabetes and elucidate if the changes seen on physical function and muscle mass can in part be explained by changes seen in cellular senescence and inflammation in blood, adipose and muscle.
2020-2022 San Antonio OAIC Scholars
Christopher Shannon, PhD
Research Project: Effects of SGLT2 Inhibition on Liver Fat and Plasma Lipidome in Older Adults
Dr. Shannon is an Assistant Professor in the Department of Medicine Diabetes Division at UT Health San Antonio. His research is broadly focused on understanding the metabolic basis of human disease, with the goal of identifying novel therapeutic approaches to combat aging, type 2 diabetes, and cancer. Chris completed his Doctorate studies in Biomedical Sciences at the University of Nottingham, UK, using nutritional and exercise-based interventions to target skeletal muscle metabolism in human aging. In 2015, Chris moved to Texas to pursue a postdoctoral position in the Diabetes Division at UT Health, studying the molecular mechanisms of insulin resistance and insulin-sensitizing therapeutics. Supported by a fellowship from the Office of Postdoctoral Affairs, Chris adopted cell and genetically modified mouse models to investigate the regulation of mitochondrial substrate fluxes in liver and adipose tissues. These studies uncovered novel mechanisms of mitochondrial remodeling during the pathogenesis of metabolic liver disease that were targetable with insulin-sensitizing drugs. Building upon these data and drawing on his cross-training in preclinical and translational studies, Chris will now use the RL5 award to study hepatic metabolism in older adults with insulin resistance. Pilot trials at the San Antonio Pepper Center are currently exploring whether the pleiotropic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, a glucose-lowering class of drugs for the treatment of type 2 diabetes, can be repurposed to improve biomarkers of aging in humans. As part of these efforts, Dr. Shannon’s project will evaluate the impact of SGLT2 inhibition on hepatic and plasma lipids in an aging population at high risk of developing metabolic liver disease.
Gustavo Almeida, PhD
Research Project: Effect of prehabilitation blood-flow restriction training on muscle function in older adults with knee osteoarthritis awaiting total knee replacement: A Pilot Randomized Controlled Trial
Dr. Almeida received his PT degree and training in Brazil and has 20 years of clinical experience with focus in Sports and Orthopedics Rehabilitation. He obtained his PhD in Rehabilitation Science from the University of Pittsburgh in 2015 and currently serves as an Assistant Professor in the Department of Physical Therapy at UT Health San Antonio. His research focuses on interventions to improve physical function and activity in individuals with arthritis. More specifically, Dr. Almeida is currently testing the feasibility of using blood-flow restriction during prehabilitation in individuals awaiting total knee replacement.
2019-2021 San Antonio OAIC Scholars
Mitzi Gonzales, PhD
Research Project: Pilot investigation of the role of cellular senescence on gait dysfunction in Alzheimer’s disease
Mitzi Gonzales is an Assistant Professor of Neurology and the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disorders, who specializes in clinical neuropsychology. Her research broadly focuses on identifying mechanisms and biomarkers of advanced age-related cognitive decline and dementia in effort to aid timely diagnosis, prevent progression, and advance treatment discovery. Dr. Gonzales earned her PhD in Clinical Psychology from The University of Texas at Austin. She completed her pre-doctoral internship at the University of Illinois at Chicago and postdoctoral fellowship in Clinical Neuropsychology at the VA Northern California Health Care System. Dr. Gonzales joined UT Health as a clinical faculty member in 2017. Since her arrival, she has been the recipient of two pilot awards including a translational neuroscience project supported by the Center of Biomedical Neuroscience. Leveraging upon this pilot award, Dr. Gonzales’ RL5 project evaluates senolytic treatment as a novel intervention for reducing gait dysfunction in Alzheimer’s disease. Pre-clinical studies have demonstrated the combination of dasatinib and quercetin cleared senescent cells and decreased tau accumulation, diminished white matter hyperintensities, and rescued aberrant cerebral blood flow. As inflammation, tau accumulation, and altered cerebral blood flow have been linked to gait abnormalities, senolytic treatment may have efficacy for restoring gait dysfunction and improving functional status in Alzheimer’s disease. As an RL5 scholar, Dr. Gonzales will participate in a mentored translational research program across the fields of clinical neuroscience, biology of aging, and clinical trial design to advance her long-term career objective of developing interventions to modulate the pathophysiology of Alzheimer’s disease and attenuate the rate of age-related cognitive decline.
Jia Nie, PhD
Research Project: Effect of Aging and mTOR Inhibition on Islet Cell Molecular Profiling in Marmosets
Jia Nie, PhD is a postdoc fellow at UT Health San Antonio in the Barshop Institute for Longevity and Aging Studies. She earned her PhD in Biochemistry and Molecular Biology through a joint dissertation between Pennsylvania State University Hershey Medical Center and Nanjing Medical University. She was awarded an American Federation for Aging Research (AFAR) Postdoctoral Transition Award in Aging. Her studies focus on islet biology and metabolic diseases. Her predoctoral research demonstrates a serine/threonine protein kinase that is most closely related to the AMPK kinase mediates insulin secretion and incretin response in islet β-cells. In 2016, Dr. Nie earned a postdoctoral position on the NIA T32 Biology of Aging Training Grant at the Barshop Institute. Aging is the universal contributor to the etiologies of metabolic decline and related diseases, including type 2 diabetes. Clinical cases had reported the remission of human type 2 diabetes is possible but is dependent upon the capacity of islet function. During the T32 training period, her project aimed at identifying how pancreatic islet dysfunction contributes to the metabolic disease progression in older populations and developing therapies to prevent metabolic diseases of aging. By performing single-cell transcriptomic atlas of healthy mouse islets, she found that each cell types within islet at each life stage have different markers and functional characteristics and that age can shift the composition of islet cells contributing to aging progression. In her RL5 project, she will use the common marmoset (Callithrix jacchus) to determine changes in islets molecular profiles during aging, evaluate the contribution of these molecular changes to metabolic disease, and test the effects of lifespan-extending interventions on pancreatic islets. This RL5 opportunity will allow her to develop a unique niche, which can directly translate findings from basic studies to primates, with hope to improve the prevention and treatment of metabolic disease in older adults.
Rozmin B. Jiwani, PhD, RN
Research Project: Effect of Behavioral Intervention on Frailty in Older Adults with Type 2 Diabetes
Rozmin B. Jiwani, PhD, RN, is an Assistant Professor at the UT Health at San Antonio School of Nursing and has just completed her second year of post-doctoral fellowship at the Geriatrics Research, Education, and Clinical Center (GRECC) at the South Texas Veterans Health Care System. During the fellow-ship she received mentoring from Dr. Espinoza on her NIH R01 funded clinical trial to examine metformin as a potential prevention of physical frailty in older adults with pre-diabetes. Working with Dr. Espinoza, she has been exposed to several other clinical studies and has also gained experience in human subject safety principles and the regulatory process. During the fellowship, her research interests evolved on testing a behavioral lifestyle intervention for overweight/obese older adults with T2D using mobile health tools to enhance self-monitoring of diet and physical activity to prevent or delay the onset of frailty and to manage T2D.
In 2013, she completed her PhD in the field of cardiovascular disease for the high-risk South Asian population, where she explored and measured illness perceptions, coping behaviors, and appraisal in 102 South Asians with coronary artery disease using a mixed methods approach. She modified and translated her dissertation questionnaires into Urdu and Hindi (the prominent languages of South Asians). Her dissertation findings brought to the forefront issues related to traditional diet, sedentary lifestyle, and stress as the modifiable risk factors for their coronary artery disease. In 2015, she completed a yearlong post-doctoral fellowship from the National Institute of Health Funded Health Disparities Steps Toward Academic Research (STAR) Program at the University of North Texas Health Science Center, Center of Excellence on Health Disparities. Completion of this fellowship has fostered her research career to community leaders, and stakeholders committed to addressing health disparities. She has extensive clinical experience as an advanced practice nurse and registered nurse in the field of chronic disease in the adult population. Her program of research is focused on health promotion and disease prevention in the field of cardiovascular diseases and diabetes in vulnerable populations.
Her RL5 project aims to determine the feasibility of a behavioral lifestyle intervention using smartphones for the self-monitoring of diet and physical activity for the improvement of frailty measurements (primary outcome) and on weight management and glycemic control (secondary outcomes) in the overweight/obese community-dwelling older adults with T2D. As a junior investigator in a transdisciplinary research project, working with experienced mentors and gaining mentored career development will provide her with exceptional training experiences that she would otherwise not receive. Dr. Jiwani will continue her pursuit of attaining her long-term career goal for becoming an independent researcher in the clinical and translational field of developing and disseminating interventions to prevent and manage frailty and diabetes complications in community-dwelling older adults.
Robyn M. Scherber, MD, MPH
Research Project: The effects of nutritional ketosis in aging and age-associated chronic myeloid hematopoietic cancers
Dr. Scherber completed her medical training at Chicago Medical School, her residency in Internal Medicine at the Mayo Clinic in Arizona, and her fellowship at Oregon Health and Science University. She currently has her clinic focusing on chronic myeloid blood malignancies, particularly among elderly patients, at the UT Health San Antonio MD Anderson Cancer Center. Dr Scherber is an active researcher focusing on the biology of clonal blood cell development, inflammation, and symptom burden among patients with chronic blood cancers. Dr. Robyn Scherber has had over a decade of research experience in this area. Her portfolio of research experience has included the development of patient reported outcome measures (i.e., MPN-SAF and MPN-10), identification of unmet patient needs (i.e., MEASURE trial), and evaluation of mechanisms for improving quality of life and symptom burden among this population (i.e., FATIGUE project, NUTRIENT Trial). In addition, she has helped develop novel treatment strategies to improve inflammation and quality of life among patients with chronic blood cancers. These efforts include conducting investigational trials that evaluate the impact of both integrative care and pharmacologic interventions. Dr. Scherber has an extensive publication record including first author publications in JCO and Blood and has won numerous research awards.
2017-2019 San Antonio OAIC Scholars
Grace C. Lee, PharmD, PhD
Research Project: Metformin to improve vaccine response and prolong healthspan in the elderly
Grace C. Lee, PharmD, PhD, is an Assistant Professor with The University of Texas at Austin College of Pharmacy and Adjunct Professor with UT Health San Antonio. She received her Doctor of Pharmacy degree from the University of the Pacific, Thomas J. Long School of Pharmacy. After completing her residency training, Dr. Lee began her position as an infectious diseases pharmacist at Kaiser Permanente in Northern California where she helped establish a regional antimicrobial stewardship program. In 2016, Dr. Lee received her PhD in Translational Science through a joint program between UT Health San Antonio, UT Austin, and the University of Texas San Antonio. Dr. Lee joined the UT Austin faculty in Fall 2016. Dr. Lee’s research has focused on the prevention and management of infectious diseases in older adults. Her RL5 project aims to determine whether metformin can improve the immune response to pneumococcal vaccines in older adults.
Miranda E. Orr, PhD
Research project: The Effects of NAD Modulation on Cognitive Aging
Miranda E. Orr, PhD is currently an Assistant Professor in the Department of Internal Medicine, Section of Gerontology and Geriatric Medicine at Wake Forest University and was formerly an Instructor at UT Health San Antonio in the Department of Pharmacology and the Sam and Ann Barshop Institute for Longevity and Aging Studies. Dr. Orr’s research focuses on cognitive aging and Alzheimer’s disease pathogenesis. She earned her PhD in Neuroscience through a joint dissertation between Montana State University and the McLaughlin Research Institute for Biomedical Research, a mouse genetics facility renowned for their neurodegenerative disease mouse models. As a predoctoral student, she was a recipient of an NIA F31 Individual Predoctoral Fellowship, National Research Service Award and NIH COBRE Center for Structural and Functional Neuroscience Award. Her work provided fundamental evidence for the utility of “patient derived stem cells” to study Alzheimer’s disease pathogenesis. In 2012, Dr. Orr earned a postdoctoral position on the NIA T32 Biology of Aging Training Grant at the Barshop Institute. She gained expertise in testing cognitive behavior and pharmacological interventions in Alzheimer’s disease mouse models, and investigated mechanisms of healthy brain aging using the longest-lived rodent known, the naked mole-rat. In 2016, Dr. Orr joined the UT Health faculty. She recently received two awards, one for basic research: Nathan Shock Transformative Pilot Award in Basic Aging, and one for translational research: Claude D. Pepper Center Pilot Award. Dr. Orr is using these resources to apply discoveries in basic science to human studies, which is the foundation of her RL5 project. Preclinical research has demonstrated that sustained NAD(+) levels is critical for the maintenance of healthy brain aging and overall lifespan in animal models. During her RL5, Dr. Orr tested whether therapies that boost NAD(+) levels can enhance cognition in healthy older individuals and those with cognitive impairment. Through this program, Dr. Orr will continue her pursuit in attaining her long-term career goal: find interventions that improve brain aging, and ultimately discover effective treatments for Alzheimer’s disease.
Lisa Kilpela, PhD
Research project: Healthy Weight Intervention Among Aging Women: An Investigation into the Role of Aging on Intervention Efficacy
Lisa Smith Kilpela, PhD, is an Assistant Professor in the Department of Psychiatry at UT Health San Antonio, and is a member of the Research to Advance Community Health (ReACH) Center. Dr. Kilpela is a licensed clinical psychologist, and she received her PhD in clinical psychology from Emory University. She completed her clinical internship at Duke University Medical Center and her postdoctoral research fellowship at Trinity University on a multi-site R01 investigating eating disorders prevention in athletes. Dr. Kilpela’s research focuses on the assessment, prevention, and treatment of eating and weight disorders. Her previous research includes investigation into the base rates and negative health consequences of dysregulated eating behaviors and body dissatisfaction in women across the lifespan. Dr. Kilpela is particularly interested in the evaluation and treatment of dysregulated eating and weight control behaviors in older populations, as well as negative health and wellness outcomes associated with these behaviors. The primary objectives of her project are to: 1) identify the unique psychological, behavioral, and endocrinological characteristics associated with dysregulated eating and weight control behaviors in older women, including health/wellness correlates (e.g., sleep, exercise, mood, quality of life); and 2) investigate the efficacy, acceptability, and feasibility of a behavioral intervention for dysregulated eating among older women.
Dr. Kilpela’s selection as a San Antonio OAIC scholar reflects the Center’s dedication to the identification of efficacious and effective interventions to improve the health, wellness, and longevity of older Americans. She continues this work as principal investigator of a Beeson Award K76AG060003.
2015-2017 San Antonio OAIC Scholars
Corinna Ross, PhD
Research Project: The effects of chronic rapamycin treatment on motor and cognitive functionin a nonhuman primate model of aging, common marmosets.
Dr. Ross is a basic scientist with a career trajectory that is leading to an emphasis on translational research, with a clear connection to clinical research in aging. Her career development plan reflects this position. Her project continued her ongoing work and moves more centrally to the theme of emphasis of the San Antonio OAIC. Dr. Ross serves as the Director of the Marmoset Aging Center. She organized a special marmosets training section for the American Society of Primatology annual meeting and was selected by FASEB to present the webinar “Animal Research: Still Necessary for Understanding Human Disease.”
The work builds on the observations made earlier in mice, that a pure pharmaceutical, rapamycin, can reproducibly extend lifespan. This seminal observation set in motion a vast array of investigations in many labs. In particular, it became evident that it would be essential to study rapamycin in nonhuman primates. Whatever the fundamental mechanisms of action of rapamycin, it will be necessary to show that these mechanisms work in primates. In primates investigational studies can be done that are impossible in humans. Therefore there is a clear path from basic observations on standard lab model organisms via nonhuman primates to human subjects.
Sukeshi Patel, MD
Research Project: A study to evaluate proteostasis modulation with histone deacetylase (HDAC) inhibitors as potential aging modulating agents in cancer patients.
In this project, Dr. Patel is studying the action of a histone deacetylase (HDAC) inhibitor on indicators of the rate of aging in patients with metastatic colorectal cancer.
Dr. Patel represents an important developing area at UT Health San Antonio, geriatric oncology. While cancer strikes the older population disproportionately, most basic and clinical studies in cancer research are of younger individuals. It is vital to understand the changing biology of cancer in older individuals and to appreciate how these changes impact the effectiveness of therapeutic strategies. Moreover, an emerging concept is that drugs used to treat cancer may act as “gerontogens” – named by analogy with carcinogens, to indicate compounds that can actually cause aging, or change the basic rate of aging.
Dr. Patel’s selection as a OAIC KL2 scholar recognizes that clinician-scientists will be needed to advance the field of geriatric oncology by bridging the gap between basic biology (of both aging and cancer) and the clinical approach to the treatment of cancer in the older individual. Understanding the full potential of the action of chemotherapeutic drugs will need this breadth of understanding.
Kelly Reveles, PharmD, PhD
Research Project: Comparison of gut microbiota composition and inflammation in elderly proton pump inhibitor-users and non-users.
Dr. Reveles’ selection as a San Antonio OAIC Scholar reflects the focus of the Center on pharmacological interventions as modulators of human biology that may impact the rate of aging. The unique aspect of this focus is the potential modulation of aging via the gut microbiota. The importance of the microbiota in all aspects of human biology is now being fully realized. Interactions between gut bacteria and diet constituents (including pharmaceuticals) influence many aspects of the immune, endocrine and other physiological systems. Simultaneously these physiological systems can regulate the microbiota. The extensive interactions between the microbiota and the human body are beginning to be realized, but the full extent remains to be discovered. It is quite within the bounds of possibility that we will find that the microbiota actually affect fundamental aging processes – indeed, in C. elegans there is already evidence that this occurs.
The second focus of Dr. Reveles’ research is the class of drugs known as proton pump inhibitors, PPIs, available over the counter and consumed in huge amounts by Americans. The increasing use of these drugs is fueled by the prevailing assumption that long term use of these drugs is safe. However, the lack of stomach acid secondarily affects the colonization of the small intestine by bacteria and subsequently affects the much larger number of bacteria in the colon. The long-term consequences are unknown. Changes to a less favorable mix of species resulting from the change in stomach acid could conceivably have multiple long term adverse effects that involve fundamental aging processes, as Dr. Reveles describes in her project.