Avrom J Caplan PhD

graduate programs : Biochemistry and Biology (Molecular cellular and developmental biology)

office: Marshak J713, 212-650 8614
lab: Marshak J719/J723

Research

1. Integrating genomics research into the undergraduate curriculum across CUNY

This is a collaborative venture with Professor Theodore Muth at Brooklyn College. Our goal is to characterize the urban metagenome in New York City.  Undergraduate students perform the work by collecting samples and analyzing them as part of their biology or microbiology classes. This work is funded by the National Science Foundation.  For more details see:

http://www.nsf.gov/awardsearch/showAward?AWD_ID=1323225

2. Protein quality control in the Cytosol
Quality control processes regulate protein homeostasis by promoting polypeptide folding, degradation and in some cases controlled aggregation. Polypeptide folding is mediated by molecular chaperones that interact with exposed hydrophobic surfaces. This reduces aggregation but can also result in targeting towards the ubiquitin/proteasome machinery for degradation. As humans age there is down-regulation of quality control systems that inversely correlates with onset of neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease. In addition, molecular chaperones buffer phenotypic change during development, regulate the onset of tumorigenesis and appear to have a general role in cellular robustness.

Our studies utilized a yeast model system to analyze the fate of newly made polypeptides; to determine the mechanisms underlying whether they will fold or be targeted towards the degradation machinery.

A second approach was the study of Hsp90 molecular chaperone inhibitors in the treatment of cancer. These inhibitors are currently in clinical trials because of their ability to stimulate degradation of several different oncogenic protein kinases. Our studies analyzed the mechanisms underlying this effect and investigate how such inhibitors come to be more effective in cancer cells than in cells from healthy tissue. We used mammalian cell culture models for these studies.

Administration

Avrom Caplan currently serves as the CUNY Associate University Dean for Research.

Recent publications

Sultana, R, Theodoraki, M. A. and Caplan, A. J. (2013). Specificity in the actions of the UBR1 ubiquitin ligase in nuclear receptor degradation. FEBS Open Bio. 3, 394-397.

Theodoraki, M.A., Nillegoda, N.B., Saini, J. and Caplan, A.J. (2012). A Network of Ubiquitin Ligases is Important for the Dynamics of Misfolded Protein Aggregates in Yeast. J. Biol. Chem. 287, 23911-22

Theodoraki, M. A. and Caplan, A. J. (2012). Quality Control and Fate Determination of Hsp90 Client Proteins.  Biochemica et Biophyscia Acta. 1823, 683-8.

Sultana, R., Theodoraki, M. and Caplan, A. J. (2012). UBR1 promotes protein kinase quality control and sensitizes cells to Hsp90 inhibition. Experimental Cell Research, 318, 53-60

Mandal, A. K., Theodoraki, M. A., Nillegoda, N. B. and Caplan, A. J. (2011).  Role of Molecular Chaperones in Biogenesis of the Protein Kinome. Methods in Molecular Biology. 787, 75-81

Nillegoda, N. B., Theodoraki, M. A., Mandal, A. K., Mayo, K. J. Ren, H. Y., Sultana, R., Wu, K., Johnson, J., Cyr, D. M. and Caplan, A. J. (2010). Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins. Mol. Biol. Cell, 21, 2102-2116

Mandal, A. K., Gibney, P. A., Nillegoda, N. B., Theodoraki, M. A., Caplan, A. J. and Morano, K. A. (2010). Hsp110 chaperones control differential fate determination of clients of the Hsp70/Hsp90 chaperone system. Mol. Biol. Cell.  21, 1439-1448.

Mandal, A. K., Nillegoda, N. B., Chen, J. A. and Caplan, A. J. (2008). Ydj1   protects nascent protein kinases from degradation and controls the rate of their maturation.  Mol. Cell Biol. 28, 4434-4444.  Recommended pick by   the Faculty of 1000 (Biology)