- Lasker Tenure Track Investigator, NIDDK, NIH, 2015-present
- Assistant Clinical Investigator, NIDDK, NIH, 2012–2015
- M.H.Sc., Duke University, 2011
- Senior Fellow, NIDDK, NIH, 2008–2012
- Fellow, NICHD, NIH, 2005–2008
- Resident, Rainbow Babies and Children’s Hospital, 2002–2005
- M.D., Mayo Medical School, 2002
Our goal is to understand the basic mechanisms regulating energy metabolism in humans. We use rare diseases as models to understand perturbations in pathways regulating energy metabolism and apply what we learn from rare diseases to common diseases and conditions such as obesity and the metabolic syndrome.
Our group studies pathophysiology and clinical therapeutics for rare disorders of extreme insulin resistance including lipodystrophy, mutations of the insulin receptor, and autoimmune conditions affecting insulin signaling. We are particularly interested in understanding the mechanisms of action of the adipokine, leptin, in improving metabolic disease in lipodystrophy.
Applying our Research
We conduct clinical trials to study new treatments for rare diseases, thereby improving the health of individuals with these rare conditions. In addition, we hope to apply what we learn from treating rare diseases to improve health in people with common conditions.
Need for Further Study
Further study is needed to understand the mechanism of action of leptin in treatment of lipodystrophy and other disorders of extreme insulin resistance.
- Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy.
- Brown RJ, Valencia A, Startzell M, Cochran E, Walter PJ, Garraffo HM, Cai H, Gharib AM, Ouwerkerk R, Courville AB, Bernstein S, Brychta RJ, Chen KY, Walter M, Auh S, Gorden P.
- J Clin Invest (2018 Aug 1) 128:3504-3516. Abstract/Full Text
- Free fatty acid processing diverges in human pathologic insulin resistance conditions.
- Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ.
- J Clin Invest (2020 Jul 1) 130:3592-3602. Abstract/Full Text
Research in Plain Language
We study patients who have rare, extreme forms of insulin resistance, meaning that the body produces the hormone insulin, but insulin does not work properly to control blood sugars. Examples of these diseases are
- lipodystrophy, which is loss of fatty tissues in parts of the body;
- mutations—permanent changes—in an insulin receptor, which is an area on the outer part of a cell that binds to insulin;
- autoantibodies—antibodies directed to one’s self—to the insulin receptors; and
- other related problems.
We use a variety of different treatments for these conditions, including treatment with the hormone leptin. Leptin is made by fat, and is low or missing in people with lipodystrophy. Treatment with leptin can improve diabetes, high cholesterol, and other medical problems in people with lipodystrophy. We are trying to understand how leptin works to improve health in lipodystrophy and other diseases.