Aditya Misra Email & Phone Number

Cambridge, Ma, Us

Cambridge, Massachusetts, United States

Pioneered innovative experimental and computational methodologies (including machine learning and multiplexed imaging) to investigate the impact of acute and chronic inflammation on tissue metabolism and resident immune cells in mouse models of bacterial sepsis and colitis. Mentored 4 undergraduate and graduate trainees.• Utilized machine learning techniques and introduced Metabolic Set Enrichment Analysis (MSEA) to pinpoint liver metabolites correlating with differential survival in a mouse model of bacterial sepsis. Notably, identified defects in the metabolism of three amino acids, leading to ~250% improvement in survival upon supplementation.• Elucidated protective mechanism of action through Density Functional Theory (DFT) studies and in vitro assays (e.g. UV-Vis, LC-MS, MTT), demonstrating amino acid byproducts neutralize pathogenic extracellular peroxides through decarboxylation reactions.• Collaborated with external laboratories to advance liquid chromatography-mass spectrometry (LC-MS) methodologies of serum from bacterial sepsis and COVID-19 patients, revealing non-survivors shared the same amino acid pathway defects.• Established novel co-culture, explant, and metabolic assays to elucidate how hits modulate inflammatory hepatocyte, macrophage, and neutrophil cross-talk. Developed TNT-FARM (see below) to synthesize nanoparticles that perturbed crosstalk in vivo. • Developed in MATLAB ODE-based mathematical models along with in vitro co-culture assays to elucidate the intricate dynamics of epithelial cell-macrophage crosstalk during colitis. Unveiled that activation of a bistable metabolic program in macrophages was crucial for the formation of protective tolerogenic memory.• Led in silico docking studies (e.g. benchmarking AlphaFold, ESMFold against HPepDock) and high-throughput assay development to design peptide libraries that modulate metabolism. Lead candidates demonstrated efficacy in mouse models of chronic inflammation.

Cambridge, Ma

Professor Arup Chakraborty's Computational Immunology LabUsing mathematical models and approaches rooted in statistical mechanics to investigate immunological systems and dynamics.• Elucidated with sequence data resolution the role of spatial heterogeneity in host immune response (derived from HIV vaccination) on intra-host HIV evolution and the resulting differential control of infection.• Extended quorum sensing model of T cell activation and developed differential equation model to suggest that inappropriate competition between self-reactive and non-self-reactive clones during immune cell reconstitution following lymphopenia leads to T cell receptor (TCR) repertoire skew characteristically found in patients with newly onset autoimmunity.

Professor Fernando Escobedo's Computational Materials and Polymers LabStarted developing computational skill set by combining molecular dynamics techniques using LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) to model DNA-coated nanoparticles and used Monte Carlo Simulations to study their respective single-stranded DNA hybridization behavior.

Dept. Of Biomedical Engineering

Professor David Putnam's Functional Biomaterials and Drug Delivery Laboratory:Independent work in Bioprocess Engineering of Immuno-modulatory materials:-Designed and optimized bio-reactor process surrounding bacterial outer membrane vesicle (OMV) vaccine platform, scaling up from a bench-scale 40mL shake flask batch process to 2L bio-reactor fed-batch process -Designed and optimized both formulations and lyophilization (freeze-drying) processes to prevent OMV storage degradation and to possibly eliminate OMV's need for cold chain.-Designed new fusion proteins for more energy-efficient membrane translocation of antigen. Independent work in Formulation Engineering towards fusion of OMVs for multivalent vaccines:-used experiments with pH shifts of OMV formulation to characterize fusion vs. aggregation of OMV particles in combination with mathematical models derived from DLVO colloid theory -explained above phenomena using molecular dynamics to show how extracellular lipopolysaccharide (LPS) serves as a counterion sinkIndependent work in Polymer Chemistry and Engineering:-Designing, synthesizing, and characterizing hydrogels for cosmetic implants-Synthesis of electrostatic binding architectures for biomimetic lubricating brush polymer

Ithaca, Ny

Philosophy of the course is for students to study the chemical and physical principles governing plant signalling and immune responses towards exploring various complex social issues surrounding natural resources and develop a creative, novel solution for each of them:-Developed and implemented new course module to incorporate lab activities for the course. Taught students dissection, electron microscopy (scanning, transmission), polarized light microscopy, small-molecule synthesis of procaine from benzocaine thru microwave ovens.-Helped students with coursework, from reading primary literature to using organic chemistry relevant for biosynthesis of small-molecules and polymer chemistry to editing and reviewing their final essays describing their solutions

Columbia Center For Translational Immunology

Dr. Megan Sykes' Bone Marrow Transplantation, Xenotransplantation Tolerance, Organ Allograft Tolerance Induction, and Type 1 Diabetes Laboratory:Involved in four separate projects:-Utilized humanized mouse model with mixed chimerism to study mechanisms driving GVHD/autoimmunity phenotype using flow cytometric techniques (presented at FOCIS 2017)-Developed cell culture protocol to expand pediatric human thymic epithelial cells and used 2-photon confocal microscopy and flow cytometry to characterize cell culture and marker phenotype (presented at International Xenotransplantation Association 2017)-Developed hydrophobicity analysis in R for T-cell receptor (TCR) sequencing data to correlate with self-reactivity (manuscript in preparation)-Proposed a mathematical model to quantify thymic export given T-cell receptor excision circle (TREC) data and the experimental ramifications of doing so. In collaboration with Dr. Andrew Yates (University of Glasgow, ARUK Chair of Mathematical Immunology and Rheumatology)

Massachusetts General Hospital, Center For Transplantation Sciences

Dr. Laurence Turka's Regulatory T Cell and Immune Cell Metabolism Laboratory:Involved in two separate projects.Utilized in vivo transplantation tolerance models to study the roles of two critical proteins in regulatory T cell function (MyD88 and PTEN). -Using flow cytometric techniques, characterized phenotype and quantified cell population changes through time.-Using a combination of in vitro cell culture and flow cytometric techniques, quantified functional marker changes in response to activation conditions.

Doctor Of Philosophy - Phd, Medical Engineering And Medical Physics

Dissertation: Tissue-Encoded Design Principles of Host Defense (under supervision of Dr. Roni Nowarski). Secured ~$500K in funding.

Chemical Engineering, Biomedical/Medical Engineering, Magna Cum Laude

High School Diploma