In our research, we are interested in understanding the balance between protein synthesis and degradation during aging. We are focusing especially on the role of the proteasome and the proteasome-ubiquitin pathway in this process. In the context of aging, we would like to understand the function of the proteasome in endoplasmic reticulum assisted degradation (ERAD) and the unfolded protein response (UPR). Particularly intriguing is the connection between ERAD and antigen processing and presentation in which the proteasome plays a major role. Additionally, we are examining the interplay between the proteasome and autophagy and its dynamics during aging.
We hypothesize that by manipulating the proteasome's pathway activity and specificity we can influence the intracellular protein balance and help cells overcome a protein folding crisis, which may play a key part in the progression of aging.
We are vitally interested in designing, synthesis and testing of small compounds that can influence the proteasome catalytic specificity and activity, and the balance between distinct forms of the proteasome. Our methods span biochemistry, organic chemistry, structural biology and a broad range of spectroscopic techniques.
Beyond aging studies, we are interested in understanding how proteins work and how they can be manipulated using atomic force microscopy. This technology allows following large protein complexes, other macromolecules, and even cells and tissue at the nanometer resolution when they are still alive with minimal stress under the native-like conditions.
Osmulski PA and Gaczynska M: (2013) Rapamycin allosterically inhibits the proteasome. Mol Pharmacol. 84(1): 104-13.
Edrey YE, Medina DX, Gaczynska M, Osmulski PA, Oddo S, Caccamo A, and Buffenstein R: (2013) Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease. Neurobiol Aging. 34(10): 2352-60.
Chen CL, Mahalingam D, Osmulski P, Jadhav RR, Wang CM, Leach RJ, Chang TC, Weitman SD, Kumar AP, Sun L, Gaczynska ME, Thompson IM, and Huang TH: (2013) Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate. 73(8): 813-26.