Eitan Akirav, PhD
Academic Faculty Appointments
Assistant Professor of Medicine
222 Station Plaza North Suite 300
Dr. Akirav earned his B.Sc. degree (Summa Cum Laude) from Tel Aviv University in Israel. Following his graduation, Dr. Akirav joined the laboratory of Dr. Mladen Vranic for his M.Sc. training at the University of Toronto focusing on the role of leptin in type 1 diabetes. In 2003, Dr. Akirav joined the Department of Immunobiology at Yale University School of Medicine as a PhD candidate where he received his training in the laboratory of Dr. Nancy H. Ruddle. There, Dr. Akirav focused on the study of regulatory T cells in a mouse model of multiple sclerosis and on the selection and maturation of T cells in the thymus. Upon graduation, Dr. Akirav joined the laboratory of Dr. Kevan Herold as a postdoctoral fellow where he has focused on the islet endothelium and its role in the function and mass of insulin producing beta cells i. Currently Dr. Akirav serves a Research Scientist at Winthrop University Hospital focusing on the effects of increased metabolic stress and reduced beta cell function on the islet microvasculator and its implications on beta cell function and mass. In addition, Dr. Akirav has developed a novel way for the detection of beta cell death through a blood derived biomarker. Dr. Akirav’s work has been published in international journals such Diabetes, Nature Reviews Endocrinology, Metabolism, Endocrinology, and more. Dr. Akirav has written several book chapters and review articles in the fields of diabetes, metabolism, inflammation.
Description of Research Interests/Activities
Dr. Akirav's research interests are focused on understanding the role of the islet microvasculature in the control of beta cell function, proliferation, and mass under the conditions of metabolic stress and inflammation. The development of glucose intolerance is largely attribute to increased insulin resistance in the periphery with reduce insulin output from the pancreas. It is therefore imperative to understand the factors that control beta cell health under both physiological and pathological conditions. We have previously shown that inflammation and hyperglycemia can both contribute to changes in the islet microvasculature density. In type 1 diabetes, a gradual reduction in endothelial cell density is associated with reduced beta cell mass and function, while treating autoimmunity and increasing metabolic demand can increase microvasculature density and improve beta cell function. Similarly, increased metabolic demand and body weight result in increased endothelial cell density while imapred metabolic control and hyperglycemia are associated with acute endothelial cell loss in type 2 diabetes. Our lab is interested in defining the origin and nature of novel anthropogenic factors that arise during impaired metabolic control and inflammation.
In addition to the study of the islet microvasculature, our lab is developing a novel method for using beta cell derived DNA in the circulation for the detection of beta cell death. We are currently improving our detection ability and conducting additional studies to apply this novel approach human patients with type 1, type 2 and gestational diabetes.
Areas of Experience
Most relevant to the current appliaction:
1. Inouye K, Chan O, Riddell MC, Akirav E, Matthews SG, Vranic M. (2002) Mechanisms of impaired hypothalamic-pituitary-adrenal (HPA) function in diabetes: reduced counterregulatory responsiveness to hypoglycaemia.
Diabetes Nutr Metab.;15(5):348-55
2. Akirav EM, Chan O, Inouye K, Riddell MC, Matthews SG, Vranic M. (2004) Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats.
3. Chan O, Inouye K, Akirav E, Park E, Riddell MC, Vranic M, Matthews SG. (2005) Insulin alone increases hypothalamo-pituitary-adrenal activity, and diabetes lowers peak stress responses. Endocrinology.146(3):1382-90
4. Chan O, Inouye KE, Akirav EM, Park E, Riddell MC, Matthews SG, Vranic M. (2005) Hyperglycemia does not increase basal hypothalamo-pituitary-adrenal activity in diabetes, but it does impair the HPA response to insulin-induced
hypoglycemia. Am J Physiol Regul Integr Comp Physiol. 289(1) R235-46
5. Akirav EM, Kushner JA and Herold KC. (2008) Beta cell mass and Type 1 diabetes: going, going, gone? Diabetes. 57(11):2883-8. Review. PMCID: PMC2570380
6. Akirav EM, Baquero MT, Opare-Addo LW, Akirav M, Glavan E, Kushner JA, Rimm DL, and Herold KC. (2011) Glucose and inflammation control islet vasculature density and beta cell function in non-obese diabetic mice.
Diabetes, in press..
7. Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM, Herold KC.Detection of beta cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011
Additional recent publications of importance to the field (in chronological order)
1. Inouye KE, Yue JT, Chan O, Kim T, Akirav EM, Park E, Riddell MC, Burdett E, Matthews SG, Vranic M. (2006) Effects of insulin treatment without and with recurrent hypoglycemia on hypoglycemic counterregulation and adrenal
catecholamine-synthesizing enzymes in diabetic rats. Endocrinology.
2. Chen Y, Akirav EM, Chen W, Henegariu O, Moser B, Desai D, Shen JM, Webster JC, Andrews RC, Mjalli AM, Rothlein R, Schmidt AM, Clynes R, Herold KC. (2008) RAGE ligation affects T cell activation and controls T cell
differentiation. J. Immunol. 181(6):4272-8. PMCID: PMC2643976.147(4):1860-70.
3. Akirav EM, Bergman CM, Hill M, Ruddle NH. (2009) Depletion of CD4(+)CD25(+) T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens. J Neurosci Res. 87(15):3511-9.
4. Ruddle NH, Akirav EM. (2009) Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response. J Immunol. 15;183(4):2205-12. PMCID: PMC2766168.
5. Akirav EM, Ruddle NH, Herold KC. (2010) The role of AIRE in human autoimmune disease. Nature Rev. Endocrinology. 7(1):25-33.
1. Eitan M Akirav and Kevan C. Herold. Stem Cell Therapy for Diabetes / editor, Shimon Efrat. Edition: 1st ed. Publisher: Springer, Chapter 12.
2. Eitan Akirav, Shan Laio and Nancy H. Ruddle. Fundamental immunology / editor, William E. Paul. Edition: 6th ed. Publisher: Philadelphia: Lippincott Williams & Wilkins, Chapter 3.
Our lab is expanding. Please contact Dr. Akirav by email if you are interested in postdoctoral or research assistant positions. Thank you!