NALINI SANTANAM, PHD, MPH, FAHA
Department of Biomedical Sciences
Prof. Department of Cardiology (Medicine)
Coordinator, Cardiovascular Disease Research cluster
1700 3rd Ave, 435S BBSC
Joan C. Edwards School of Medicine, Marshall University
Huntington, WV 25755
Redox Regulation of Cardiometabolic Diseases
Cardiometabolic diseases are on the rise within the United States especially in the Appalachian region (West Virginia- 2nd highest). Cardiometabolic diseases (CMD) includes obesity, Type 2 diabetes and cardiovascular diseases. Lifestyle modifications (diet and exercise) can help to reduce risk to CMD by regulating appetite and preventing metabolic dysfunction. Regulating redox stress is a key mechanism by which lifestyle modifications prevent CMD. Altering the gut-microbiome axis may also be involved. Our research utilizes novel stress-less mouse models (BBA 1863:2293-2306) to alter redox balance and improve appetite and microbiota. We are studying the effects of diets (high saturated, PUFA or omega-3 fatty acid rich diets) or exercise on appetite regulation (adipose-brain-liver cross-talk), gut microbiota and cardiometabolic endpoints in these mouse models. ECHO-MRI, CLAMS, rodent treadmills, rodent ultrasound, next generation sequencing, miRNA microarray, Luminex technology, Ingenuity pathway analysis etc are some of the cutting edge techniques that are routinely used in our studies.
Aging and Adipose Dysfunction
Aging increases risk to cardiometabolic diseases especially cardiovascular disease, insulin resistance leading to diabetes. Studies have shown a loss of adipose function with aging. Our studies using Aging rat models (Fischer 344 x Brown Norway hybrid rats-FBN) showed sex dependent changes in ectopic fat adipokine profile. Our studies further showed a loss in metabolic plasticity in preadipocytes (adipose derived stem cells) with aging. MicroRNAs that regulated adipocyte differentiation were dysfunctional (PLoS One, 2013, 8(3):e59238, J Physiol & Biochem, 2017, 73:215-224). Our NIH (NIA) funded study investigates the association between increased risk to insulin resistance during aging to changes in pathways that regulate microRNA biogenesis and function in the adipose tissue.
Epicardial Fat and Vascular Cross Talk
Cardiovascular disease rates are still highest in the Appalachian region. These high rates are attributed to high prevalence of obesity within this region. Increase in visceral/abdominal adiposity is a hallmark for obesity. However, increase in ectopic fat (deposition of fat in non-adipose tissue) increases risk to obesity-associated complications (coronary artery disease, insulin resistance, non-alcoholic fatty liver disease, etc). Increase in fat that surrounds the heart or vasculature (epicardial fat) is a marker for future cardiovascular events (Images to the Left and Right). Studies in our laboratory are investigating the role of epicardial/perivascular fat (the fat that surrounds the heart and the coronaries) in risk to cardiovascular diseases in animal models and humans with coronary artery disease (CAD) (in collaboration with Department Thoracic Surgery). We are investigating the role of microRNA and epigenetic pathways in adipose dysfunction. Epicardial fat-cardiomyocyte cross talk studies are being conducted using animal models and ex-vivo cell culture models.
Epigenetics In Endometriosis and Ovarian Cancer
Endometriosis is an inflammatory/epigenetic disorder affecting about 10% of young women. The classic symptoms are infertility and chronic pelvic pain. Typically this pain is treated with non-steroidal anti-inflammatory drugs (NSAIDs), or with drugs that address the hormonal aspects of the disorder. Research from our laboratory over the past 20 years has shown the importance of oxidative stress in the etiology of both endometriosis and its associated pain (Pain, 2015, 156(3):528-39; Redox Biol, 2017, 12:956-966). Our clinical studies have shown the beneficial effects of antioxidant therapy (Vitamin E & C) in lowering the pain associated with endometriosis (Transl Res. 2013;161(3):189-95; Reprod. Sci. 2017;24:619-626). In collaboration with the Department of Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University we are investigating mechanisms involved in endometriosis-associated pain with the hope of uncovering more effective treatment options. We are using novel techniques in the fields of redox biology and epigenetics to produce new therapeutic options (Image to the Left)
Endometriosis increases risk to ovarian cancer. In collaboration with the Edwards Comprehensive Cancer Center, Marshall University, we are studying the role of peritoneal microenvironment on endometriosis related ovarian cancer (Annals Transl Med. 2020). We are studying epigenetic pathways that link endometriosis and ovarian cancer (Image to the Right).
TRANSLATIONAL STUDIES IN PROGRESS
1. Epicardial Fat Biomarkers: WV-Appalachian Heart Study. In collaboration with Department of Cardiothoracic Surgery, St. Mary’s Heart Center, Huntington, WV.
2. Epigenetics, Oxidative Stress and Endometriosis associated pain: In collaboration with Department of Gynecology and Obstetrics, Cabell Huntington Hospital, Huntington, WV.
3. Novel biomarkers & Technology Based Intervention In Diabetic Patients (TEACH Clinical Trial): In collaboration with Department of Endocrinology (Medicine) and Appalachian Translational Research Network.
4. Role of epigenetics in endometriosis associated ovarian cancer: In collaboration with Edwards Comprehensive Cancer Center.
1. Ray K2, Fahrmann J2, Mitchell B, Paul D, King H#, Crain C#, Cook C, Golovko M, S. Brose#, S. Golovko and Santanam N. Oxidation-sensitive nociception involved in endometriosis associated pain. (2015) Pain, 156(3):528-39.
2. Kristeena Ray Wright2a, Brenda Mitchell, Nalini Santanam. Redox regulation of microRNAs in endometriosis-associated pain. (2017) Redox Biology, 12:956-966.
3. Deborah L. Amos2, Tanner Robinson#, Melissa B. Massie#, Carla Cook, Alexis Hoffsted#, Courtney Crain4, Nalini Santanam. Overexpression of catalase modulates metabolic parameters in leptin-deficient mice. (2017) BBA Molecular Basis of Disease 1863:2293-220. doi: 10.1016/j.bbadis.2017.06.016.
4. Deborah L. Amos2, Carla Cook, Nalini Santanam. Omega 3 Rich Diet Modulates Energy Metabolism via GPR120-Nrf2 crosstalk in a Novel Antioxidant Mouse Model. (2019) BBA (Molecular and Cell Biology of Lipids) 1864(4):466-488.
5. Sarah Brunty2, Nalini Santanam. Current assessment of the (dys)function of macrophages in endometriosis and its associated pain. (2019) Annals Transl Med. Dec 7(Suppl 8):S381 DOI: 10.21037/atm.2019.12.119.
6. Sarah Brunty2, Brenda Mitchell, Nadim Bou-Zgheib, Nalini Santanam. Endometriosis and ovarian cancer risk, an epigenetic connection. Annals Transl Med. 2020.
7. Sabel Meadows, Abbagael Seidler, Madison Wall, Jamika Page, Cara Taylor, Brendin Flinn, Robin Turner, and Nalini Santanam. Altered regulation of adipomiRs editing with aging. (2020) J. Mol. Sci. (2020) Sep 20:21(18):6899.
1. Dr. Nalini Santanam, PhD, MPH, FAHA –Professor
2. Sarah Binion- 4th year PhD Student - PhRMA funded
3. Brendin Flinn (UG student)- NASA funded
4. Cara Hively (UG Student) – First2 Student- WV-INBRE funded
Graduated PhD Students:
1. Kristeena Ray Wright, PhD (May 2017) Post-Doc, Harvard University, Application Specialist, Advanced Instruments
2. Debbie Amos - PhD (May 2019) -Faculty, Ohio Valley University