Biography
Research Topics
Multi-Disciplinary Training Area
Research
Ubiquitin Signaling in Cancer Biology
Post-doctoral Fellow: Kenneth Wu
MD/PhD Graduate Student: Robert A. Chong
Covalent linkage of ubiquitin chains to cellular proteins leads to targeted substrate degradation by the 26S proteasome, thereby promoting unidirectional alteration of a divergent array of cellular processes, such as cell cycle progression and signal transduction, in a manner that profoundly impacts tumorigenesis.
Central to the ubiquitination reaction is the recognition of a substrate by an E3 ubiquitin protein ligase, which also functions to recruit an E2 ubiquitin-conjugating enzyme that catalyzes the transfer of ubiquitin to the target protein. Work from this laboratory has helped discover and characterize a super-family of E3s known as the cullin-RING ubiquitin ligases (CRL). CRL comprises ~300 modular protein complexes (including CRL1/SCF, CRL2-5 and CRL7), nearly half of E3s in humans. Lysine 48 (K48)-polyubiquitination mediated by CRL is a predominant cellular mechanism for targeting proteins for degradation by the 26S proteasome. CRL deregulation causes protein imbalance that contributes to myriad cellular defects or disease states such as cancer.
To understand and target K48 polyubiquitination by CRL, we recently developed fluorescence (Förster) resonance energy transfer (FRET)-based cell free reporter systems that generate a specific fluorescence signal as a result of enzymatic synthesis of an ubiquitin-ubiquitin covalent linkage through K48. On the basis of this assay format, we have performed high throughput screens, resulting in identification of a diversified array of small molecule inhibitors and are currently exploring their mechanisms of action and therapeutic potentials.
In addition, fluorescence-based assays are highly sensitive, allowing direct visualization of the process of K48 ubiquitination. We are exploring this innovation to develop real time reaction models that help understand the dynamics of K48 ubiquitination, a process of fundamental importance to a living cell.
Education
PhD, Columbia University
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Industry Relationships
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their outside financial relationships.
Dr. Pan has not yet completed reporting of Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their outside financial relationships.
Dr. Pan has not yet completed reporting of Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.