Tharun Selvam Mahendran

Biophysics PhD, State University of New York at Buffalo

Buffalo, New York, United States

About

Since the beginning of my research journey in biology, I have been deeply interested in understanding the mechanistic principles underlying neurodegenerative disorders such as Alzheimer’s disease, which disproportionately affects the aging population, as well as the process of cellular aging in general. My motivation stems not only from scientific curiosity but also from a personal desire to improve the health span of older individuals. This challenge extends globally, with Alzheimer’s disease projected to impose a $2 trillion socioeconomic burden by 2030 if left unaddressed. Given the limitations of conventional therapies targeting protein aggregation, it is crucial to develop novel, multifaceted strategies to combat the disease effectively. Through my research on Alzheimer’s disease pathways, integrating cell biology and biophysics across in vivo, in cellulo, and in vitro models, I have developed a strong foundation in disease mechanisms. Moving forward, I aim to design and implement therapeutic approaches targeting Alzheimer’s pathogenesis as well as aging-associated morbidities. I seek to expand my expertise in genome-scale engineering and drug delivery biotechnologies, alongside leadership skills, to contribute to the next generation of therapeutics for aging-related disorders.

Experience

  • University at Buffalo (Full-time · 5 yrs 5 mos)
    • Graduate Research Assistant
      Jun 2022 - May 2026 · 4 yrs

    • Graduate Teaching Assistant
      Jan 2021 - May 2022 · 1 yr 5 mos

      I. BIO315 Biochemistry lab (offered in the spring 2022 semester) II. BIO329 Genetics lab (offered in the fall 2021 semester) III. BIO211 Cell biology lab (offered in the spring 2021 semester) • Demonstrated laboratory practices and experimental techniques to at least 150 students • Designed online quizzes and graded over 160 lab reports • Conducted office hours twice a week during semesters to help students with assignments • Administered and graded over 80 individual practical examinations

    • Graduate Student Researcher
      Jan 2021 - May 2022 · 1 yr 5 mos

  • JNCASR (2 yrs)
    • Junior Research Fellow
      Jun 2019 - Nov 2020 · 1 yr 6 mos

      I. Elucidated the biological target of a peptide modulator of autophagy-induced α-synuclein degradation • Demonstrated that a peptide modulator of autophagy operates in an NFκB-dependent manner to facilitate α-synuclein degradation in cellulo • Conducted immunofluorescence-based and live-cell colocalization experiments of fluorescently labeled autophagy markers and α-synuclein to assess α-synuclein degradation kinetics • Performed nucleo-cytoplasmic fractionation and immunoblotting to show NFκB nuclear translocation and concomitant PTM status upon treatment with the peptide modulator of autophagy • Designed siRNA for NFκB gene silencing experiments and primers for generating novel plasmid constructs • Mentored two undergraduate students for over a year; both have gone on to pursue competitive postgraduate programs II. Investigated the role of putative Plasmodium falciparum autophagy-related proteins through heterologous expression in S. cerevisiae knockout strains • Confirmed that the Plasmodium falciparum ortholog of yeast Atg12 indeed functions similarly to yeast Atg12 in facilitating the function of the Atg8 conjugation system required in autophagosome biogenesis • Performed complementation experiments in S. cerevisiae to test the function of putative Plasmodium autophagy proteins (PfAtg12, PfAtg5) by the transformation of Atg12Δ/Atg5Δ yeast strain, using live-cell fluorescence microscopy • Designed codon harmonized PfAtg5 sequence using bioinformatics tools and cloned the sequence into yeast 2μ and pcDNA 3.1 plasmids for expression in yeast and mammalian cell lines, respectively • Developed an ImageJ macro-based image analysis pipeline to quantify the number of puncta and colocalization events from yeast immunofluorescence images in a batch process

    • Visiting Fellow
      Dec 2018 - May 2019 · 6 mos

      I. Inspected the effect of soluble tau (4R0N isoform) expression on endocytic vesicular dynamics and APP trafficking implicated in amyloid-β (Aβ) formation • Showed that soluble tau impairs endocytic trafficking in terms of vesicle motility, displacement, and turnover, as well as the translocation of an endocytic cargo, Amyloid Precursor Protein (APP), implicated in amyloid-β (Aβ) formation • Conducted live-cell imaging to capture trafficking of endocytic vesicles and quantified trafficking dynamics using TrackMate • Conducted immunofluorescence-based colocalization experiments to track endocytic vesicle maturation and turnover • Prepared the full-length manuscript, now published in Frontiers in Aging Neuroscience, including representative fluorescence photomicrographs, graphs, and all written sections • Designed project hypothesis and performed the entirety of experiments relevant to the publication IV. Surveyed potency of an autophagy-inducing drug on the R6/2 mouse model of Huntington's disease in the clearance of huntingtin aggregates in the brain • Assessed the status of drug-induced autophagic degradation of huntingtin aggregates using immunohistochemistry of fixed mouse brain sections to label autophagy protein markers and huntingtin aggregates for colocalization studies using confocal fluorescence microscopy • Carried out transcardial perfusion of mice for fixation of the whole brain, and cryotome sectioning of the fixed mouse brain to segregate cortical and hippocampal brain sections for immunohistochemistry

  • Trainee at Orchid Chemicals and Pharmaceuticals Private Limited
    Sep 2018 - Sep 2018 · 1 mo

    Studied the proceedings of Active Pharmaceutical Ingredient (API) manufacturing, and design aspects of a drug manufacturing plant.

  • Undergraduate Student Researcher at SRM University
    Sep 2017 - Apr 2018 · 8 mos

    I. Characterized a xenoestrogen-induced Drosophila melanogaster model of autism spectrum disorder (ASD) and tested the effect of Cerium Oxide nanoparticle treatment in curbing disease symptoms • Correlated Bisphenol-A exposure to flies to induction of locomotive deficits, social behavior abnormalities, and elevated oxidative stress, symptoms characteristic of ASD. Treatment of diseased flies with Cerium Oxide nanoparticles alleviates these symptoms • Established a xenoestrogen (Bisphenol-A) induced Drosophila melanogaster model of autism spectrum disorder using behavioral (larval crawling, negative geotaxis, courtship) and biochemical assays (lipid peroxidation), and histological assays (oxidative stress markers) • Designed a fly-tracking chamber based on an extensive literature survey, to ascertain fly locomotive behavior in terms of velocity, trajectory, and position • Maintained stocks of Oregon K strain D. melanogaster

  • Intern at LifeCell International Pvt.Ltd
    Jun 2017 - Jun 2017 · 1 mo

    I. Monitored and organized protocols for the isolation of adult stem cells from umbilical cord blood and tissue, and menstrual blood, as well as the segregation of desired stem cell populations using FACS II. Handled customer relationship management (CRM) for at least 3000 customer profiles