Molecular investigations in the laboratory of Jochen Reiser, MD, PhD are focused on the discovery for the causes of kidney disease. Furthermore, the Reiser laboratory is developeing novel therapies and assays to combat renal diseases and its many complictaions.
Basic and translational science as well as patient studies have linked a common circulating blood protein—soluble urokinase plasminogen activator receptor (suPAR)—with chronic kidney disease risk and mechanistically to be harmful for podocytes, the filtering cells of the kidney.
Reiser’s laboratory is housed within the Department of Internal Medicine, of which he is chairperson.
In 2008 and 2011, Reiser led ground using highly collaborative team science of international researchers and scientists to discover that the uronkinase receptor and its soluble form suPAR can trigger the glomerular kidney disease Focal Segmental Glomerulosclerosis (FSGS). Based on these observations, Reiser and his collaborators went on to study whether suPAR was associated with even types of chronic kidney diseases.
As described in a November 2015 New England Journal of Medicine article, they found that a high suPAR level was an excellent predictor of future kidney disease. The researchers measured suPAR levels and kidney function (based on eGFR rates) in 2,292 people in the Emory Cardiovascular Biobank at baseline and again at follow up. Of these subjects, 40 percent of subjects with high suPAR levels (greater than 3,040 ng/mL) but no known kidney disease (i.e. healthy eGFR levels) went on to develop chronic kidney disease over the course of five years. In comparison, only 10 percent of those with low suPAR levels at baseline developed the disease. Moreover, suPAR was shown to predict eGFR decline in patients with already established earlier stage kidney disease as well.
Reiser and his team continue to explore additional research questions around suPAR and kidney disease. They are also involved in early work by a biopharmaceutical company to develop novel drug therapies that would neutralize suPAR.
Other projects in the laboratory are geared to understand the cellular behavior of podocytes as well as their injury response. For that, the Reiser laboratory uses genetic, metabolic as well as general molecular biology techniques to decipher important new insights into human health in the largely unmet medical need area of kidney disease.
Dr. Reiser’s laboratory has constantly been funded by the National Institutes of Health, Health Foundations and other intra and extramural funding agencies.
American Society of Clinical Investigation (ASCI), (Rush Institutional Representative)
American Clinical and Climatological Association (ACCA)
Association of American Physicians (AAP)
Dr. Reiser is the author of more than 150 medical and scientific articles. A complete list of his journal articles can be found on PubMed.
Reiser J, Polu KR, Moller 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. 2005;37:739-44.
Sever S, Altintas MM, Nankoe SR, Moller CC, Ko D, Wei C, Henderson J, del Re E, Hsing L, Erickson A, Cohen CD, Kretzler M, Kerjaschki D, Rudensky A, Nikolic B, Reiser J. Proteolytic processing of dynamin by cytoplasmic cathepsin L defines a mechanism for proteinuric kidney disease. J Clin Invest. 2007;117:2095-104. Comments at Science 2007, 317:872 and J Clin Invest. 2007;117:2079-2082.
Wei C, Möller CC, Altintas MM, Li J, Schwarz K, Zacchigna S, Xie L, 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. 2008;14:55-63.
Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14:931-938.
Fornoni A*, Sagheshima J, Wei C, Saenz M, Robier AP, Jauregui AN, Li J, Mattiazzi A, Ciancio G, Chen L, Zilerulello G, Carolyn A, Jayanthi C, Wacheree S, Ricordi C, Ikehata M, Rastaldi MP, Reiser J* and Burke GW*. Rituximab prevention of recurrent focal segmental glomerulosclerosis is associated with podocyte protection via sphingomyelination Science Translational Medicine 2011 *co-correspondence author. Jun 1;3(85):85ra46. (Cover of journal)
Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J, Maiguel D, Karumanchi SA, Yap HK, Saleem M, Zhang, Q, Nikolic B, Chaudhuri A, Daftarian P, Salido E, Torres A, Salifu M, Sarwal M, Schaefer F, Morath C, Schwenger V, Zeier M, Gupta V, Roth D, Rastaldi MP, Burge GW, Ruiz P, Reiser J. Circulating urokinase receptor as a cause for focal segmental glomerulosclerosis Nat Med. 2011 Jul 31;17(8):952-60. doi: 10.1038/nm.2411. (Cover of Journal)
Yaddanapudi S, Altintas MM, Kistler A, Fernandez I, Möller CC, Wei C, Peev V, Flesche JB, Forst AL, Li J, Patrakka J, Xiao Z, Grahammer F, Schiffer M, Lohmüller T, Reinheckel T, Gu C, Huber TB, Ju W, Bitzer M, Rastaldi MP, Ruiz P, Tryggvason K, Shaw A, 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. 2011 Sep 12. pii: 58552. doi: 10.1172/JCI58552. [Epub ahead of print].
Schiffer M, Teng B, Gu C, Shchedrina VA, Kasaikina M, Pham VA, Hanke N, Rong S, Gueler F, Schroder P, Tossidou I, Park JK, Staggs L, Haller H, Erschow S, Hilfiker-Kleiner D, Wei C, Chen C, Tardi N, Hakroush S, Selig MK, Vasilyev A, Merscher S, Reiser J, Sever S. Pharmacological targeting of actin-dependent dynamin oligomerization amerliorates chronic kidney disease in diverse animal models. Nat Med., 2015; 21:601-609 (PMID: 25962121)
Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S, Altintas MM, Wei C, Hotton AL, French AL, Sperling LS, Kerakis S, Quyyumi AA, Reiser J. Soluble Urokinase Receptor and Chronic Kidney Disease. NEJM 2015, DOI: 10.1056/NEJMoa1506362
Jochen Reiser, MD, PhD
The Ralph C. Brown, MD, Professor
Chairperson, Department of Internal Medicine
Rush University Medical Center
1653 W. Congress Parkway
1017D Kellogg
Chicago, IL 60612
Phone: (312) 942-3163
Email: jochen_reiser@rush.edu