PhD in pharmaceutical sciences with a specialization in computational drug design, North Dakota State University, Fargo, North Dakota
Master of Technology in information technology with a specialization in bioinformatics, Indian Institute of Information Technology, Allahabad, India
Bachelor of Pharmacy, The Tamil Nadu Dr. MGR Medical University, Chennai, India
Diploma in Pharmacy, Thanjavur Medical College, Thanjavur, India
Fellowships & Additional Training
Post-doctoral fellow, Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont
Natesan teaches the following courses:
PharDSci 528: Pharmacokinetics
PharmSci 573: Principles of Pharmacokinetics and Toxicokinetics
PharmSci 571: Computer-Aided Drug Design (CADD)
Natesan’s primary research interests are in the area of computational drug design, investigating drug action and disposition through mathematical modeling and simulation. His laboratory’s research goals are directed towards two important aspects of preclinical drug discovery:
- Modeling protein-ligand, protein-peptide interactions using state-of-the-art structure- and ligand-based techniques such as molecular docking, pharmacophore-based virtual screening, quantitative structure-activity, and structure-property relationships, molecular dynamics simulation, and hybrid QM/MM methods.
- Developing in silico predictive models for membrane-drug and membrane-protein-drug interactions at atomistic details using combined MD simulation techniques and novel surrogate systems. These models will provide fast and efficient ways to screen and design new therapeutics with desired pharmacokinetic and pharmacodynamic properties.
He also actively collaborates with clinical pharmacists in developing population-based pharmacokinetic (PBPK) models for optimizing antibiotic therapies.
Honors & Awards
- Chancellor’s Excellence in Teaching Award, 2021
- Cetero, PRACS Institute/James D. Carlson Graduate Student Research Excellence Award, 2009
- NSF-North Dakota-EPSCoR Doctoral Dissertation Fellowship, 2008 – 2010
- Institute Silver Medal, Indian Institute of Information Technology, Allahabad, UP, India, 2006
- Ministry of Human Resource Development, Government of India Graduate Research Scholarship, 2004-2006
Washington Research Foundation Phase 1 Technology Commercialization Grant (2021-2022)
Allosteric modulators of µ-opioid receptors as potential therapeutics in pain
NIH/NIGMS -R01 GM137022-01 – (2020-2024)
Molecular biophysics of integrin activation by oxysterols and rational discovery of small-molecular modulators
NIH/NIGMS – R15 GM131293-01 (9/20/2018 – 08/31/2021)
Specifics of “Non-Specific Membrane Interactions” of Drugs: An Integrated Approach for Understanding Structure-Membrane Interaction Relationships.
NIH/NINDS – R41 NS107099-01 (09/01/2018 – 08/31/2019)
In Silico Identification of Novel GHB Receptor Ligands for SSADH Deficiency, a Disorder of GABA Metabolism.
Role: PI, in collaboration with Speragen Inc.
NIH/NIAID – R01 AI083387-07A1 (08/01/2018 – 07/31/2022)
Molecular and cellular mechanism regulating innate immunity and inflammation during pattern recognition receptor activation and respiratory virus infection.
Role: Co-I, in collaboration with Dr. Santanu Bose (PI)
GC, Jeevan; Chen, Justin; Pokharel, Swechha; Mohanty, Indira; Mariasoosai, Charles; Obi, Peter; Panipinto, Paul; Bandyopadhyay, Smarajit; Bose, Santanu; Natesan, Senthil. Molecular basis for the recognition of 24-(S)-hydroxycholesterol by integrin αvβ3. Scientific Reports 2023, 13(1):9166.
GC, Jeevan; Szlenk, Christopher; Diyaolu, Ayobami; Obi, Peter; Gibson K M.; Natesan, Senthil; Roullet, Jean-Baptiste. Allosteric modulation of GABAA receptor by Farnesol. Biophysical Journal. 2023, 122, 1-19.
Obi, Peter; Natesan, Senthil. Membrane lipids are an integral part of transmembrane allosteric sites in GPCRs: A case study of cannabinoid CB1 receptor bound to a negative allosteric modulator, ORG27569, and analogs. Journal of Medicinal Chemistry 2022, 65 (18), 12240-12255.
Szlenk, Christopher*; GC, Jeevan*; Natesan, Senthil. Membrane-facilitated receptor access and binding mechanisms of long-acting β2-adrenergic receptor (β2-AR) agonists. Molecular Pharmacology 2021, 100(4), 406-427.
Espiritu, Michael J.; Chen, Justin*; Yadav, Jaydeep; Larkin, Michael; Pelletier, Robert D.; Chan, Jeannine M.; GC, Jeevan B*.; Natesan, Senthil; Harrelson, John P. Mechanisms of herb-drug interactions involving cinnamon and cytochrome P450 2A6: Focus on time-dependent inhibition by cinnamaldehyde and 2-methoxycinnamaldehyde. Drug Metabolism and Disposition 2020, 48:1028-1043.
GC, Jeevan B.; Szlenk, Christopher T.; Gao, J.; Dong, X.; Wang, Z.; Natesan, Senthil. Molecular dynamics simulations provide insight into the loading efficiency of pro-resolving lipid mediators resolvin D1 and D2 in cell membrane-derived nanovesicles. Molecular Pharmaceutics 2020, 17(6), 2155-2164.
Fechtner, Sabrina; Singh, Anil K.; Srivastava, Ila, Szlenk, Christopher T.; Muench, Tim R.; Natesan, Senthil and Ahmed, Salahuddin. Cannabiboid receptor 2 agonist JWH-015 inhibits interleukin-1β-induced inflammation in rheumatoid arthritis synovial fibroblasts and in adjuvant induced arthritis rat via glucocorticoid receptor. Frontiers in Immunology: Autoimmune and Autoinflammatory Disorders. 2019, 10:1027-38
Szlenk, Christopher T.; GC, Jeevan B.; Natesan, Senthil. Does the lipid bilayer orchestrate access and binding of ligands to transmembrane orthosteric/allosteric sites of GPCRs? Molecular Pharmacology April 8, 2019, DOI: https://doi.org/10.1124/mol.118.115113
Pokharel, Swechha M.; Shil, Niraj K.; GC, Jeevan B.; Colburn, Zachary T.; Tsai, Su-Yu; Segovia, Jesus A.,; Chang, Te-Hung; Natesan, Senthil*; Jones, Jonathan C. R.*; Bose, Santanu*. Integrin activation by the lipid molecule 25-hydroxycholesterol induces a proinflammatory response. Nature Communications 2019.
*These authors jointly supervised this work.
Tian, Dan-Dan; Natesan, Senthil; White, John R.; Paine, Mary F. Effects of common CYP1A2 genotypes and other key factors on intra-individual variation in the caffeine metabolic ratio: An exploratory analysis. Clinical and Translational Science. 2019, 12(1), 39-46.
Natesan, Senthil; Pai, Manjunath P.; Lodise, Thomas. Determination of alternative ceftolozane/tazobactam (C/T) dosing regimens for patients with infections due to Pseudomonas aeruginosa with high (C/T) MIC values. J. Antimicrob. Chemoth. 2017, 72(10), 2813-2816.
Kim, Sophia; Natesan, Senthil; Cornilescu, Gabriel; Carlson, Samuel; Tonelli, Marco; McClurg Urszula L.; Binda, Olivier; Robson, Craig N.; Markley, John L.; Balaz, Stefan; and Glass, Karen C. Mechanism of histone H3K4me3 recognition by the plant homeodomain of inhibitor of growth 3. J. Biol. Chem. 2016 (doi:10.1074/jbc.M115.690651)
Natesan, Senthil; Lukacova, Viera; Peng, Ming; Subramaniam, Rajesh; Lynch, Sandra; Wang, Zhanbin; Tandlich, Roman; Balaz, Stefan.Structure-based prediction of drug distribution across the headgroup and core strata of a phospholipid bilayer using surrogate phases. Mol. Pharmaceutics. 2014, 11(10), 3577-3595
Poplawski, Amanda; Hu, Kaifeng; Lee, Woonghee; Natesan, Senthil; Peng, Danni; Carlson, Samuel; Neuhardt, Elizabeth; Shi, Xiaobing; Balaz, Stefan; Markley, John L.; Glass, Karen C. Novel molecular insights into the recognition of N-terminal histone modifications by the BRPF1 bromodomain. J. Mol. Biol. 2014, 426 (8), 1661-1676
Lukacova, Viera; Natesan, Senthil; Peng, Ming; Tandlich, Roman; Wang, Zhanbin; Lynch, Sandra; Subramaniam, Rajesh; Balaz, Stefan. Structural determinants of drug partitioning in surrogates of phosphatidylcholine bilayer strata. Mol. Pharmaceutics 2013, 10 (10), 3684–3696
Natesan, Senthil; Wang, Zhanbin; Lukacova, Viera; Peng, Ming; Subramaniam, Rajesh; Lynch, Sandra; Tandlich, Roman; Balaz, Stefan. Structural determinants of drug partitioning in n-hexadecane/water system. J. Chem. Inf. Model. 2013, 53 (6), 1424–1435
Natesan, Senthil; Balaz, Stefan. Rigorous incorporation of tautomers, ionization species, and different binding modes into ligand-based and receptor-based 3D-QSAR methods. Curr. Pharm. Design 2013, 19(23), 4316-4322
Natesan, Senthil; Subramaniam, Rajesh; Bergeron, Charles; Balaz, Stefan. Binding affinity prediction for ligands and receptors forming tautomers and ionization species: Inhibition of mitogen-activated protein kinase-activated protein kinase 2 (MK2) inhibitors. J. Med. Chem. 2012, 55 (5), 2035–2047
Natesan, Senthil; Wang, Tiansheng; Khandelwal, Akash; Lukacova, Viera; Bartus, Vladimir; Subramaniam, Rajesh; Balaz, Stefan. Cell-QSAR: Conceptual dissection of receptor binding and intracellular disposition in antifilarial activities of Selwood antimycins. J. Med. Chem. 2012, 55(8), 3699-3712
Natesan, Senthil; Wang, Tiansheng; Khandelwal, Akash; Lukacova, Viera; Bartus, Vladimir; Balaz, Stefan. Rigorous treatment of multi-species multi-mode ligand-receptor interactions in 3D-QSAR: CoMFA analysis of thyroxine analogs binding to transthyretin. J. Chem. Inf. Model. 2011, 51 (5), 1132-1150