Murugappan (Modi) Sathappa
Foxboro,MA
Summary
Biochemist/Biophysicist with 14+ years of experience in expression, purification, and biophysical/biochemical characterization of soluble and membrane proteins. Expertise in protein-protein/peptide, protein-small molecule, peptide/protein-lipid interactions progressing the early drug discovery research.
Core competencies:
- Demonstrated success in leading protein sciences group and designing/executing biochemical/biophysical assays for multiple programs.
- Experience managing CRO resources (FFS & FTE model) for protein science and structural biology work
- Experience leading biochemistry/biophysics group in fast-paced environment
- Conscientious team player and collaborator with exemplary observational, analytical and communication skills.
Overview
12
12
years of professional experience
Work History
Principal Scientist (Senior Scientist)
Kymera Therapeutics, Lead Discovery
05.2022 - Current
- Headed multiple hit finding campaigns for various targets as team lead and project lead
- Designed biochemical/biophysical assays for mechanistic understanding of ternary complex formation, ubiquitination and degradation of lead heterobifunctional molecules
- Spearheaded discovery of novel molecular glue for immunology target
- Managed direct reports in experimental designs and prioritization of strategies
- Managed communication with external CROs for protein production, biochemical/biophysical assays and crystallography work.
Senior Scientist (Scientist II)
Syros Pharmaceuticals, Biochemistry and Biophysics
07.2020 - 04.2022
- Biochemistry/Biophysics functional lead responsible for developing assays for HTS and characterizing novel protein-protein interactions in the Sickle Cell Disease program
- Developed various biophysical assays like SPR (ABA-mode), TR-FRET, FP, DSF, and ITC in-house for validating hits targeting these novel protein-protein interactions
- Designed various protein constructs that are critical for assay development and structural work
- Spearheaded design of fluorescence-based thiol quenching assay to enable SAR for covalent fragments
- Managed communication with external CROs for protein production, analytical ultracentrifugation (AUC), Native & HDX-MS, and crystallography work
- Managed direct reports in experimental design and evaluating new technologies for biophysics/biochemistry group.
Research Scientist I
Broad Institute, CDoT, Protein Sci And Struct Bio
03.2017 - 06.2020
- Designed and developed enzymatic assay in-house for HTS
- Developed and characterized interaction of protein with small-molecule inhibitors identified from initial screen using SPR, ITC, DSC, and other fluorescent-based assays
- Spearheaded protein science division of collaborative project for identification of small molecule inhibitors of target oncoprotein
- Designed and engineered novel constructs for expression and purification of oncoprotein for obtaining high-resolution crystal structure
- Cloned, expressed, purified antigen binding fragments (Fabs) for co-crystallization studies and characterized Fabs-protein interactions (epitope binning) using BLI
- Initiated semi-automation workflow for small-scale test expressions in different host systems.
Graduate Research Assistant
University of Connecticut
08.2011 - 02.2017
- Characterized mechanism of action of drug Elamipretide (Bendavia) in treating Barth Syndrome in collaboration with Dr.Hazel Szeto (Founder of Stealth Biotherapeutics)
- Developed use of novel nanoscale bilayer systems (membrane scaffolding protein (MSP) and styrene-maleic acid (SMA) copolymer bound nanodiscs of purified OXPHOS enzyme cytochrome c oxidase).
Education
Ph.D - Biochemistry
University of Connecticut
Storrs, CT02.2017
M.S - Biochemistry
University of Connecticut
Storrs, CT05.2011
B.Tech - Biotechnology
SASTRA University
Tanjore, India05.2009
Skills
- Biochemistry and Biophysics: Differential scanning fluorimetry; Isothermal titration and Differential scanning calorimetry; Microscale Thermophoresis; Surface Plasmon Resonance; Biolayer Interferometry (BLI); Caliper Mobility-Shift Assay; steady-state and time-resolved fluorescence spectroscopy and anisotropy; electrokinetic measurements; seahorse cell analysis; stopped-flow enzyme kinetics; UV/visible and CD spectroscopy
- Protein Science: Bacterial, yeast, Baculovirus and Mammalian protein expressions (Membrane and soluble protein expression); AKTA purification - size exclusion, affinity, IEX & SEC, multi-angle (SEC-MALS) and dynamic light scattering (DLS)
- Molecular biology: Immunoblotting; site-specific protein labeling; in-vitro transcription and cell-free protein synthesis; molecular cloning; site-directed cross-linking and co-immunoprecipitation; Real Time-PCR; site-directed mutagenesis; plasmid preparation; DNA/RNA extraction
- Computational: Swiss PDB Viewer; PyMOL; MOE; Maestro (Schrodinger)
Additional Information
- Pre-Doctoral and Doctoral Dissertation Fellowship, for performing outstanding research.
- Richard C. Crain, Jr. Memorial Fellowship for demonstrating academic promise and established research in the field of Biochemistry.
- Poster Travel Stipend Award, Barth Syndrome Foundation.
- Best Poster Award, North Eastern Structure Symposium.
- Spot Awards (2), Center for the Development of Therapeutics, Broad Institute,
- Spot Award, Syros Pharmaceuticals
- Leo Award(2), Kymera Therapeutics
PEER-REVIEWED PUBLICATIONS
●Malhotra K, Sathappa M, Landin JS, Johnson AE, Alder NN. Nat. Struct. Mol. Biol. 20: 965-72. (2013)
✔ Article highlighted as a News and Views “Voltage-coupled conformational dynamics of a mitochondrial protein-import channel” in the same issue. “Peering into the Protein Pathways of a Cell” in UConn Today, University of Connecticut, July 8, 2013. Science Daily, Biology News Net and Eureka Alert.
●Baile MG, Sathappa M, Lu YW, Pryce E, Whited K, McCaffery JM, Han X, Alder NN, Claypool SM. J. Biol. Chem. 289: 1768-78. (2014)
●Sathappa M, Alder NN. Biochimica Et Biophysica Acta (BBA)-Biomembranes. 1858(6), 1362-1372 (2016)
●Sathappa M, Alder NN. Bioprotocols Bio-protocol 6(22): e2030 (2016)
●Mitchell W, Emily A, Tamucci JD, Boyd K, Sathappa M, et al. J.Biol.Chem. 295(21):7452-7469 (2020)
●Persky NS, Hernandez D, Do Carmo M, Brenan L, Cohen O, Kitajima S, Nayar U, Walker A, Pantel S, Lee Y, Cordova J, Sathappa M et al. Nat. Struct. Mol. Biol. 27, 92-104 (2020)
●Reidenbach, A. G., Mesleh, M. F., Casalena, D., Vallabh, S. M., Dahlin, J. L., Leed, A. J., Minikel. et.al J.Biol.Chem. 295(39):13516-13531 (2020)
●Miller PG*, Sathappa M*, Moroco JA*, Jiang W, Yue Q et.al Nat Commun 13, 3778 (2022)
Timeline
Principal Scientist (Senior Scientist)
Kymera Therapeutics, Lead Discovery
05.2022 - Current
Senior Scientist (Scientist II)
Syros Pharmaceuticals, Biochemistry and Biophysics
07.2020 - 04.2022
Research Scientist I
Broad Institute, CDoT, Protein Sci And Struct Bio
03.2017 - 06.2020
Graduate Research Assistant
University of Connecticut
08.2011 - 02.2017
Ph.D - Biochemistry
University of Connecticut
M.S - Biochemistry
University of Connecticut
B.Tech - Biotechnology
SASTRA University
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