Heather Ferris

Heather Ferris, MD, PhD

Heather Ferris, MD, PhD, Assistant Professor of Medicine

Training:

  • 1998 B.A., Chemistry, B.S., Biochemistry, College of Charleston
  • 2005 Ph.D., Molecular Physiology an Biological Physics, University of Virginia
  • 2006 M.D., University of Virginia
  • 2009 Residency, University of Pittsburgh Medical Center
  • 2012 Endocrinology Fellowship, Beth Israel Deaconess/Joslin Diabetes Center
  • 2012-2017 Instructor, Harvard Medical School, Research Associate, Joslin Diabetes Center
  • Ferris Clinical Practice (https://uvahealth.com/findadoctor/profile/heather-a-ferris)

Research in the Ferris Lab:

People living with Type 2 diabetes are at increased risk for cognitive decline and Alzheimer’s disease. Our research uses both cell and animal models to study the impact of diabetes on the brain. In particular, we are interested in:

1. How insulin regulates cholesterol synthesis in the different cell types of the brain and how this impacts brain energetics and function.

2. The potential role of oxidized cholesterol species as signaling molecules in the brain in diabetes and Alzheimer’s disease.

3. Understanding the role of insulin in the pathogenesis of Alzheimer’s disease.

 Cholesterol metabolism in the brain is unique from the periphery. Cholesterol is unable to cross the blood brain barrier so the brain produces its own supply. In addition, the blood brain barrier regulates insulin access to the brain. Insulin receptor activation contributes to the synthesis of brain cholesterol. It has been observed that in the diabetic mouse there is an impairment of cholesterol synthesis and this is mediated by insulin deficiency. We have followed up on these studies, knocking out the key transcriptional regulator of cholesterol, SREBP2, in the main cholesterol synthesizing cells of the brain, the astrocytes.

We find that loss of cholesterol synthesis by astrocytes leads to an increase in brain glucose metabolism, resulting in altered whole body metabolism in the animals. In addition, alterations in brain lipid oxidation result in circadian rhythm disruptions. We are currently investigating the underlying mechanisms of these circadian rhythm disruptions as well as exploring altered cholesterol synthesis in other cells of the brain.

 There are currently clinical trials using intranasal insulin to attempt to modify Alzheimer’s disease progression. The mechanisms that may be driving these changes are currently unclear. We are interested in better defining the targets of intranasal insulin with the thought that there may be more efficient or specific ways to activate the desired pathways for improved clinical outcome. These studies are being conducted using cell culture in combination with insulin receptor knockout and Alzheimer’s disease mouse models.

Contact Us:

Heather Ferris, MD, Ph.D.

Assistant Professor of Medicine

Division of Endocrinology and Metabolism

PO Box 801406

Charlottesville, VA 22908

Lab location: MR4, Room 6022

Lab phone: 434-924-5473

hf4f@virginia.edu

Link to publications by Dr. Ferris

Kulas JA, Weigel TK, Ferris HA, Insulin resistance and impaired lipid metabolism as a potential link between diabetes and Alzheimer’s disease., 2020; Drug development research. 81(2) 194-205. PMID: 32022298

Weigel TK, Kulas JA, Ferris HA, Oxidized cholesterol species as signaling molecules in the brain: diabetes and Alzheimer’s disease., 2020; Health psychology and behavioral medicine. 3(4) NS20190068. PMID: 32269839 | PMCID: PMC7104322

Kleinridders A, Ferris HA, Tovar S, Editorial: Crosstalk of Mitochondria With Brain Insulin and Leptin Signaling., 2019; Frontiers in endocrinology. 9() 761. PMID: 30619091 | PMCID: PMC6301996

Cai W, Xue C, Sakaguchi M, Konishi M, Shirazian A, Ferris HA, Li ME, Yu R, Kleinridders A, Pothos EN, Kahn CR, Insulin regulates astrocyte gliotransmission and modulates behavior., 2018; The Journal of clinical investigation. () . PMID: 29664737

Kleinridders A, Ferris HA, Reyzer ML, Rath M, Soto M, Manier ML, Spraggins J, Yang Z, Stanton RC, Caprioli RM, Kahn CR, Regional differences in brain glucose metabolism determined by imaging mass spectrometry., 2018; Molecular metabolism. 12() 113-121. PMID: 29681509

Ferris HA, Perry RJ, Moreira GV, Shulman GI, Horton JD, Kahn CR, Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism., 2017; Proceedings of the National Academy of Sciences of the United States of America. 114(5) 1189-1194. PMID: 28096339 | PMCID: PMC5293102

Ferris HA, Isganaitis E, Brown F, Time for an End to Juice in the Special Supplemental Nutrition Program for Women, Infants, and Children., 2017; JAMA pediatrics. () . PMID: 28437541

Ferris HA, Kahn CR, Unraveling the Paradox of Selective Insulin Resistance in the Liver: the Brain-Liver Connection., 2016; Diabetes. 65(6) 1481-3. PMID: 27222392 | PMCID: PMC4878421

Fukui K, Ferris HA, Kahn CR, Effect of cholesterol reduction on receptor signaling in neurons., 2015; The Journal of biological chemistry. 290(44) 26383-92. PMID: 26370080 | PMCID: PMC4646295

Kleinridders A, Ferris HA, Cai W, Kahn CR, Insulin action in brain regulates systemic metabolism and brain function., 2014; Diabetes. 63(7) 2232-43. PMID: 24931034 | PMCID: PMC4066341

Ferris HA, Williams G, Parker JA, Garber JR, Therapeutic implications of diffuse hepatic uptake following I-131 therapy for differentiated thyroid cancer., 2013; Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 19(2) 263-7. PMID: 23529347

Suzuki R, Ferris HA, Chee MJ, Maratos-Flier E, Kahn CR, Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function., 2013; PLoS biology. 11(4) e1001532. PMID: 23585733 | PMCID: PMC3621654

Ferris HA, Kahn CR, New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it., 2012; The Journal of clinical investigation. 122(11) 3854-7. PMID: 23093783 | PMCID: PMC3484465

Ferris H, Hunt S, Destination ventricular assist devices for heart failure #205., 2009; Journal of palliative medicine. 12(10) 956-7. PMID: 19807242

Ferris HA, Walsh HE, Stevens J, Fallest PC, Shupnik MA, Luteinizing hormone beta promoter stimulation by adenylyl cyclase and cooperation with gonadotropin-releasing hormone 1 in transgenic mice and LBetaT2 Cells., 2007; Biology of reproduction. 77(6) 1073-80. PMID: 17699734

Ferris HA, Shupnik MA, Mechanisms for pulsatile regulation of the gonadotropin subunit genes by GNRH1., 2006; Biology of reproduction. 74(6) 993-8. PMID: 16481592

Curtin D, Ferris HA, Häkli M, Gibson M, Jänne OA, Palvimo JJ, Shupnik MA, Small nuclear RING finger protein stimulates the rat luteinizing hormone-beta promoter by interacting with Sp1 and steroidogenic factor-1 and protects from androgen suppression., 2004; Molecular endocrinology (Baltimore, Md.). 18(5) 1263-76. PMID: 14988433

Haisenleder DJ, Ferris HA, Shupnik MA, The calcium component of gonadotropin-releasing hormone-stimulated luteinizing hormone subunit gene transcription is mediated by calcium/calmodulin-dependent protein kinase type II., 2003; Endocrinology. 144(6) 2409-16. PMID: 12746302

Ferris HA, Tapia JA, García LJ, Jensen RT, CCKA receptor activation stimulates p130(Cas) tyrosine phosphorylation, translocation, and association with Crk in rat pancreatic acinar cells., 1999; Biochemistry. 38(5) 1497-508. PMID: 9931015

Tapia JA, Ferris HA, Jensen RT, García LJ, Cholecystokinin activates PYK2/CAKbeta by a phospholipase C-dependent mechanism and its association with the mitogen-activated protein kinase signaling pathway in pancreatic acinar cells., 1999; The Journal of biological chemistry. 274(44) 31261-71. PMID: 10531323

Ferris HA, Carroll RE, Lorimer DL, Benya RV, Location and characterization of the human GRP receptor expressed by gastrointestinal epithelial cells., 1997; Peptides. 18(5) 663-72. PMID: 9213359

Ferris HA, Carroll RE, Rasenick MM, Benya RV, Constitutive activation of the gastrin-releasing peptide receptor expressed by the nonmalignant human colon epithelial cell line NCM460., 1997; The Journal of clinical investigation. 100(10) 2530-7. PMID: 9366567 | PMCID: PMC508453