Mehmet M. Altintas, PhD graduated in Chemical Engineering from Bogazici University, Turkey, and obtained his PhD in Biotechnology at the same University in 2001. Around that time, flux-based analysis of metabolic networks was a hot topic in the area of system biology since it leads to a detailed understanding of biochemical characteristics of organisms. During his PhD studies and post-doctoral training at the University of Colorado, he cultured and simulated the growth and production of a wide variety of organisms from bacteria to yeast and mammalian cells using the tools of fermentation engineering and metabolic engineering. After joining the laboratory of Jochen Reiser, MD, PhD, at Massachusetts General Hospital in 2004, his interest then turned to kidney podocytes. Since then, his main research has concerned the identification of molecular targets involved in the early structural changes leading to the development of proteinuria.
Altintas’s work is often interdisciplinary and combines methods from genetics, cell, molecular and system biology to address the regulation of the metabolism of kidney podocytes under normal and pathological conditions. Our experimental and theoretical analyses of metabolic alterations produced by injury or disease will ultimately lead to better understanding of kidney disease and may contribute to identification of potential new therapeutic targets and better therapeutic outcome.
Other research in the laboratory focuses on the underlying molecular mechanisms of cathepsin L (CatL) dependent regulation of podocyte structure and function. We have previously shown that activity of cytosolic CatL drives podocyte injury through proteolytic degradation of the major regulatory GTPase dynamin, podocyte marker protein synaptopodin and slit diaphragm protein CD2AP. All together, these findings opened the door for the concept of podocyte disease as enzymatic disease and led to a widespread interest in the novel truncated form of CatL.
Altintas’s research has been funded by the National Institutes of Health and other Health Foundations through grants collaboratively submitted with Jochen Reiser, MD, PhD, and his research lab.
‘The Best Dissertation’ Award, Bogazici University, Istanbul, Turkey (2002)
Altintas is the author of more than 30 medical and scientific articles. A complete list of his journal articles can be found on PubMed.
- Reiser J, Polu KR, Moeller CC, Kenlan P, Altintas MM, Wei C, Faul C, Herbert S, Villegas I, Avila-Casado C, McGee M, Sugimoto H, Brown D, Kalluri R, Mundel P, Smith PL, Clapham DE, Pollak MR. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 37:739-44, 2005.
- Altintas MM, Eddy CK, Zhang M, McMillan JD, Kompala DS. Kinetic modeling to optimize pentose fermentation in Zymomonas mobilis. Biotechnol Bioeng 94:273-95, 2006.
- Sever S, Altintas MM, Nankoe SR, Moeller CC, Ko D, Wei C, Henderson J, del Re E, Kretzler M, Cohen CD, Erickson A, Kerjaschki D, Rudensky A, Nikolic B, Reiser J. Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease. J Clin Invest 117:2095-104, 2007.
- Wei C, Moeller CC, Altintas MM, Li J, Schwarz K, Henger A, Schmid H, Kretzler M, Parrilla R, Bendayan M, Nikolic B, Kalluri R, Carmeliet P, Mundel P, Reiser J. Modification of kidney barrier function by the urokinase receptor. Nat Med 14:55-63, 2008.
- Altintas MM, Azad A, Nayer B, Contreras G, Zaias J, Faul C, Reiser J, Nayer A. Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J Lipid Res 52:480-8, 2011.
- Yaddanapudi S, Altintas MM, Kistler AD, Fernandez I, Moeller CC, Wei C, Peev V, Flesche JB, Forst AL, Li J, Patrakka J, Xiao Z, Grahammer F, Schiffer M, Lohmuller T, Reinheckel T, Gu C, Huber TB, Ju W, Bitzer M, Rastaldi MP, Ruiz P, Tryggvason K, Shaw AS, Faul C, Sever S, Reiser J. CD2AP in mouse and human podocytes controls a proteolytic program that regulates cytoskeletal structure and cellular survival. J Clin Invest 121:3965-80, 2011.
- Altintas MM, Moriwaki K, Wei C, Moller CC, Flesche J, Li J, Yaddanapudi S, Faridi MH, Godel M, Huber TB, Preston RA, Jiang JX, Kerjaschki D, Sever S, Reiser J. Reduction of proteinuria through podocyte alkalinization. J Biol Chem 289:17454-67, 2014.
- Lee HW, Khan SQ, Faridi MH, Wei C, Tardi NJ, Altintas MM, Elshabrawy HA, Mangos S, Quick KL, Sever S, Reiser J, Gupta V. A podocyte-based automated screening assay identifies protective small molecules. J Am Soc Nephrol 26:2741-52, 2015.
- Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S, Altintas MM, Wei C, Hotton AL, French AL, Sperling LS, Lerakis S, Quyyumi AA, Reiser J. Soluble urokinase receptor and chronic kidney disease. N Engl J Med 373:1916-25, 2015.
- Reiser J, Altintas MM. Podocytes. F1000Research 5(F1000 Faculty Rev):114, 2016.
Mehmet M. Altintas, PhD
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