Sidhartha Mahali, PhD

My primary research interest lies in studying, understanding and translating molecular events into cellular physiology to understand and treat neurodegenerative disorders. My academic career so far has provided me with an excellent background in understanding and studying the cell signaling pathways  associated  with  a  number  of  cellular  processes  such  as  cell  death,  autophagy- lysosomal machinery, cytoskeleton modulation and cellular metabolism. I have expertise in cell and molecular biology techniques along with expertise in qualitative and quantitative imaging by confocal microscopy. My present work in Dr. Celeste Karch’s lab is focused on stem cell models of  dominantly  inherited  AD  (DIAD).  Our  findings  suggest  that  DIAD  mutations  in  PSEN1  and PSEN2 are sufficient to cause impaired lysosome function and tau accumulation, which may drive AD pathogenesis. My previous postdoctoral research work with Dr. Mathieu Bollen was focused on the role of microtubule-associated factors (MAPs) in the regulation of mitotic events and to delineate  the  molecular  mechanism  associated  with  phospho-dephosphorylating  events.  My doctoral  research  with  Dr.  Sunil  Manna,  was  focused  on  understanding  the  AGE  (Advanced Glycation End product)-mediated cellular responses.    

AGEs normally form during aging and at an accelerating rate in diabetes. Our novel findings mapped AGE-mediated cell signaling pathways related to inflammation, cellular degeneration and metabolic deregulation, which may be prevalent in neurodegeneration and fatty liver condition seen in aging and diabetes. We were also able to identify a key rate limiting signaling pathway and a natural small molecule that is effective in protecting   AGE-mediated   metabolic   de-regulation.   My   research   career   has   focused   on understanding the role of cytoskeleton associated protein machinery in regulating different cellular processes such as cell division, intracellular transport and spatio-temporal modulation of the cell signaling pathways with neurology in prime focus. My long-term goal is to build on these skills along with additional training in stem cell biology and neuropathology in order to establish an independent research program on understanding the role of lysosomes in AD and developing novel therapeutics.

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