- B.S., Syracuse University
- B.A., Rhode Island College
- Ph.D., Brown University
BIOL 410 Biochemistry I
BIOL 654 Advanced Topics in Biology
CHEM 103H Honors General Chemistry
CHEM 106 General Organic & Biological Chem II
CHEM 310 Biochemistry I
CHEM 410 Biochemistry I
CHEM 491 Research In Chemistry
CHEM 493 Research In Chemistry
Small molecule regulators of Nicotinamide phosphoribosyltransferase (NAMPT).
: This NIH funded study focuses on the activation and pontential regulation of a critical enzyme in the NAD+ salvage pathway. Students learn how to manipulate DNA, produce and purify recombinant protein, and run biochemical activation assays. This foundation in biotechnology provides students the skills and confidence to pursue graduate or medical degrees or land industrial jobs.
NAD+ is essential for life and thus must be strictly regulated. NAD+ homeostasis has been linked to several devastating conditions that plague the American population, including but not limited to cancer, diabetes, and Alzheimer’s disease. NAD+/NADH is widely known as a cofactor in oxidation/reduction reactions, however more recently it was discovered that NAD+ is consumed during times of stress. For example, cancerous cell have an up-regulation and increased activity of poly(ADP-ribose) polymerases (PARP) and Sirtuin proteins that respond by providing increased DNA damage repair and cellular survival respectively. These protein families convert NAD+ to nicotinamide (NAM) as a byproduct of enzymatic activity. Recycling of NAM back to NAD+ is accomplished in two steps by the NAD+ salvage pathway. First, NAM is converted to nicotinamide mononucleotide (NMN) by Nicotinamide phosphoribosyltransferase (NAMPT) also called NAmPRTase, PBEF, or Vistafin. Second, NAD+ is generated by the adenylation of NMN with concomitant hydrolysis of ATP by nicotinamide nucleotide adenylyl transferase (NMNAT). NAMPT is the rate-limiting step in the NAD+ salvage pathway and has been directly linked to diseases such as cancer and inflammation.
NAMPT is a 55-kDa enzyme that forms a homodimer to generate two active sites. The channel leading into the active site is primarily housed in one monomer with contributions at the active site from the opposing monomer. Little to no information is available regarding the dimerization and thus activation of the NAMPT monomers. We hypothesize that small molecule interactions can facilitate dimer formation and thus regulate NAMPT activity. The overall goal is to determine which structural components of the two recently identified modulators are required to elicit the effect on NAMPT activity. This information can then direct the screening of drug libraries for novel regulators. We propose to 1) screen commercially available derivatives of the two known regulators and 2) establish a method to monitor the interaction based on Surface Plasmon Resonance (SPR). We anticipate identifying several new compounds that influence NAMPT activity.