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
Watertown, MA
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
Cambridge, MA
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
Cambridge, MA
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
Storrs, CT
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