We study HMGB1-mediated DNA damage, cellular senescence, and neuroinflammation as upstream drivers of Alzheimer's disease, HIV-associated dementia, and related tauopathies — with the goal of turning mechanistic insight into therapeutic action.
The Gaikwad Lab investigates the molecular events that initiate neurodegeneration — before amyloid plaques form, before tau tangles appear, before the clinical symptoms of Alzheimer's disease emerge.
Our central discovery positions nuclear HMGB1 depletion as "Phase 0" of AD pathology — the initiating event that impairs non-homologous end joining (NHEJ) DNA repair, allows double-strand breaks (DSBs) to accumulate, activates the cGAS-STING innate immune pathway, and drives neurons and glia into a pro-inflammatory senescent state that fuels tau propagation and neurodegeneration.
We combine human transcriptomic meta-analysis (snRNA-seq of ~1.5M nuclei across 176 subjects), biochemical studies in human AD brain tissue, immunofluorescence and immunoelectron microscopy, co-immunoprecipitation, and translational therapeutic development — including intranasal delivery platforms and next-generation CAR-T cell approaches — to understand and ultimately reverse neurodegeneration.
The lab is embedded within UTMB's Department of Neurobiology and benefits from close collaborations with the Sarkar Lab (Huntington's disease, mitochondrial DNA repair) and the Kayed Lab (tau oligomers and protein aggregation).
The Gaikwad Lab is actively growing. We are looking for enthusiastic scientists at all levels — from undergraduate researchers to experienced postdoctoral fellows — who are passionate about understanding and treating Alzheimer's disease and neurodegeneration.
Our lab offers a rigorous scientific environment with training in molecular biology, human brain tissue research, single-nucleus RNA sequencing analysis, immunofluorescence microscopy, preclinical mouse modeling, and cutting-edge cell therapy approaches.
We prioritize mentorship, scientific independence, and career development. Trainees are supported in grant writing, publications, and conference presentations at major venues including Alzheimer's Association International Conference (AAIC) and the Society for Neuroscience (SfN) annual meeting.