Research Interests

Kiris lab is interested in basic and translational studies in the fields of molecular neurobiology and neurodegenerative diseases, mainly utilizing mouse embryonic stem cell and human induced pluripotent stem cell-derived neuronal models.

More specifically, our current research interests include:

I. Enhancement of neurotrophin signaling against neurodegerative diseases. Neurotrophin signaling pathways are considered potential therapeutic targets in many neurodegenerative diseases, including Alzheimer's Disease, due to their roles in neuroprotection, synaptic plasticity and neurogenesis. Originating from Dr. Kiris' work in Dr. Lino Tessarollo's lab (Neural Development Group at National Cancer Institute at Frederick, NIH, USA), which focused on the in vivo dissection of neurotrophin signaling pathways by targeting specific Trk intracellular domains (Kiris et al., J. Neurosci. 2014), we are interested in modulation of Trk receptor mediated signaling against the neurodegenerative process of the diseases.

II. Molecular mechanism(s) underlying the sex-specific differences observed in neurodegenerative diseases. Previous studies implicate that neurotrophin and estrogen signaling pathways may cross-talk and thereby contribute to the sex-specific differences observed in various neurodegenerative conditions. Our research interests include studies to elucidate whether there is direct, functional, sex-specific, integrated effects of neurotrophin and estrogen signaling pathways in health and neurodegenerative diseases, using human induced pluripotent stem cell-derived neuronal models.

III. Botulinum neurotoxin (BoNT) research and drug discovery. BoNTs target motor neurons and cause life-threatening disease botulism. Currently, there are no drugs to inhibit these toxins once they are internalized into motor neurons. We have previously established drug screening and experimentation systems using mouse (Kiris et al., 2011, Stem Cell Research, Kota et al., 2014, JoVE) and human motor neurons (Kiris et al., 2015, Neurotoxicity Research) derived from embryonic stem cells. In addition to the assay development, our work also focused on identification of mechanism-targeted compounds to identify novel BoNT inhibitors. Currently, we are interested in i) elucidation of critical molecular mechanisms in motor neurons involved in intoxication and/or recovery, ii) identification of mechanism-targeted compounds to identify novel leads that can be effective against BoNT serotypes responsible for human botulism, and iii) stem cell based detection technologies for these toxins.