Thomas Weimbs

Biography

Dr. Weimbs received his doctoral degree from the Department of Biochemistry of the University of Cologne, Germany, in 1993. He conducted postdoctoral research at the Department of Anatomy, University of California at San Francisco until 1999. In the same year, he joined the Department of Cell Biology in the Lerner Research Institute of the Cleveland Clinic as an Assistant Professor where he established his research laboratory focusing on investigating membrane trafficking and epithelial cell polarity as well as molecular mechanisms underlying polycystic kidney disease. In 2005, Dr. Weimbs was recruited to the Department of Molecular, Cellular, and Developmental Biology and moved his laboratory to UCSB. Dr. Weimbs is currently an Associate Professor in MCDB and in the Neuroscience Research Institute.

Research

Research in the Weimbs Laboratory is centered around two related areas of investigation:

1. Autosomal-dominant polycystic kidney disease (ADPKD) is considered the most common life-threatening, monogenic inherited disease. ADPKD affects over 600,000 people in the US alone, is a leading cause of kidney failure, and also leads to significant cardiovascular complications. Currently, no treatment exists for this disease, and most patients require renal transplantation or life-long dialysis for survival. Research in the Weimbs Laboratory is aimed at understanding the molecular mechanisms that lead to renal cyst growth and disease progression, and to identify and test new strategies for therapy.
2. SNAREs and epithelial cell polarity: Most human cell types are "polarized", i.e. they exhibit asymmetry, which is essential to their function. This includes epithelial cells that make up most major human organs such as the kidney, liver, lungs, GI tract, exocrine glands etc. Carcinogenesis is accompanied by the progressive loss of epithelial cell polarity. Current research in the Weimbs lab is aimed at investigating novel signaling functions of so-called SNARE proteins which are essential for the establishment and maintenance of cell polarity.

Selected Publications

Dafinger C, Mandel AM, Braun A, Göbel H, Burgmaier K, Massella L, Mastrangelo A, Dötsch J, Benzing T, Weimbs T, Schermer B, Liebau MC. The carboxy-terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC-activation. J Cell Mol Med. 2020 ;24:14633–14638.

Giovannone AJ, Reales E, Bhattaram P, Nackeeran S, Monahan AB, Syed R, Weimbs T. The Habc domain of syntaxin 3 is a ubiquitin binding domain. Sci Rep. 2020 ;10(1):21350.

Strubl S, Torres JA, Spindt AK, Pellegrini H, Liebau MC, Weimbs T. STAT signaling in polycystic kidney disease. Cellular Signalling. 2020 ;72:109639.

Torres JA, Rezaei M, Broderick C, Lin L, Wang X, Hoppe B, Cowley BD, Savica V, Torres VE, Khan S, Holmes RP, Mrug M, Weimbs T. Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease. J Clin Invest. 2019 ;130:4506-4522.

Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T. Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease. Cell Metabolism. 2019 ;30:1007–1023.

Kipp KR, Kruger SL, Schimmel MF, Parker N, Shillingford JM, Leamon CP, Weimbs T. Comparison of folate-conjugated rapamycin versus unconjugated rapamycin in an orthologous mouse model of polycystic kidney disease. Am J Physiol Renal Physiol. 2018; 315:F395–F405.

Olsan EE, West JD, Torres JA, Doerr N, Weimbs T. Identification of Targets of Interleukin-13 and Signal Transducer and Activator of Transcription-6 (STAT6) Signaling in Polycystic Kidney Disease. Am J Physiol Renal Physiol. 2018; 315:F86–F96.

Giovannone AJ, Winterstein C, Bhattaram P, Reales E, Low SH, Baggs JE, Xu M, Lalli MA, Hogenesch JB, Weimbs T. Soluble syntaxin 3 functions as a transcriptional regulator. J Biol Chem. 2018; 293:5478-5491.

Weimbs T. Are Cyst-Associated Macrophages in Polycystic Kidney Disease the Equivalent to TAMs in Cancer?. J Am Soc Nephrol. 2018; 29:2447-2448.

Giovannone AJ, Reales E, Bhattaram P, Fraile-Ramos A, Weimbs T. Mono-ubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes. Mol Biol Cell. 2017; 28:2843-2853.

Soo-Hoo L, Banna CD, Radeke CM, Sharma N, Albertolle ME, Low SH, Weimbs T, Vandenberg CA. The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons. PLoS One. 2016; 11(9):e0163671.

Doerr N, Wang Y, Kipp KR, Liu G, Benza JJ, Pletnev V, Pavlov TS, Staruschenko A, Mohieldin AM, Takahashi M, Nauli SM, Weimbs T. Regulation of Polycystin-1 Function by Calmodulin Binding. PLoS One. 2016; 11(8):e0161525.

Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T. A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. Am J Physiol Renal Physiol. 2016; 310: F726 –F731.

Rothé B, Leal-Esteban L, Bernet F, Urfer S, Doerr N, Weimbs T, Iwaszkiewicz J, Constam DB. Bicc1 polymerization regulates the localization and silencing of bound mRNA. Mol Cell Biol. 2015; 35:3339-3353.

Olsan EE, Matsushita T, Rezaei M, Weimbs T. Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease. J Biol Chem. 2015; 290:15679–15686.