Education

PhD, Indian Institute of Science, 1994

MS, University of Mysore (India), 1986

BSc, University of Mysore (India), 1984

Research Interest

My research interest is to investigate how proteins interact with one another to control life processes. Proteins interact with each other in a highly specific manner, and these specific interactions play key roles in many cellular processes. In normal life processes, these protein interactions are well coordinated to perform the functions of the cells. Any deregulation of this process can lead to the development of many diseases. At present, I have three major research projects related to cell surface proteins and targeting these proteins using peptides, peptidomimetics, and grafted peptides.

EGFR heterodimerization in cancer: The goal of this project is to design molecules that inhibit EGFR dimerization and hence cell signaling in cancer. My research interest is in the structural aspects of epidermal growth factor receptor (EGFR) extracellular domains, which have important implications in cancer. Targeting both EGFR and HER2 receptors simultaneously is advantageous in treating NSCLC that exhibits resistance to current therapy. Such grafted stable peptides that are orally available will have an impact on lung cancer treatment that develops resistance and on the survival rate of lung cancer patients. For the molecules I have developed, one US patent was approved (US 2018 / 0230185 A1), and for a grafted peptide, I have applied for a US patent application (16/970,198 in 2019). This project is supported by funding from NCI (5R01CA255176).

Novel plant-based molecules for immunomodulation: Modulation of cell adhesion is essential for the suppression of immune response in autoimmune diseases, improving drug delivery through the biological barriers (i.e., intestinal mucosa and blood-brain barriers), and inhibition of tumor metastasis. Adhesion molecules or co-stimulatory molecules maintain sustained contact between T cells and the antigen-presenting cell (APC) and help the T cell receptor (TCR)-MHC interaction generates a signal for immune response. CD2 and CD58 are cell surface protein molecules (co-stimulatory molecules) that participate in the early stage of the immune response.

I have designed peptides from the CD2 protein sequence to modulate CD2-CD58 interaction. I have utilized these peptides to modulate CD2-CD58 interactions during the T-cell activation process in autoimmune diseases such as rheumatoid arthritis (RA).

Peptide conjugates as imaging agents for colorectal cancer (collaborative project): The goal of this project is to design, synthesize and investigate colon cancer cell-targeted near-infrared (near-IR) fluorophores for the in vivo imaging of colorectal cancer (CRC) in animals, and eventually in humans, including the small (< 5 mm) and flat colon cancers that are often missed by standard colonoscopy.

Teaching Interest

Drug Design and Discovery, Protein Structure and Function, Computational Methods in Drug Discovery, Medicinal Chemistry

Awards & Honors

2022, Dean’s Research Excellence Award, University of Louisiana Monroe (ULM)

2022, Researcher of the semester, ULM

2016, Research Excellence Award, ULM

2006, 2008, 2011, 2017, 2022, Teaching Excellence Award from the class of students, College of Pharmacy

2009 and 2017, Recognized at the Annual Meeting of the American Association of Colleges of Pharmacy (AACP) in Boston as one of the AACP Teachers of the Year

2003, JSPS fellowship to visit RIKEN institute (from Japan)

Publications

Jill Comeau, Kavitha Beedupalli, Seetharama Jois (2022). Lung cancer tumors with diversified genetic mutations-complications in choosing therapeutic options. Journal of Clinical and Translational Discovery Sep;2(3):e123. https://pubmed.ncbi.nlm.nih.gov/36532867/ 

Sonju, Jafrin Jobayer, Achyut Dahal, Vivitri Dewi Prasasty, Prajesh Shrestha, Yong‐Yu Liu, and Seetharama D. Jois (2022). Assessment of Antitumor and Antiproliferative Efficacy and Detection of Protein‐Protein Interactions in Cancer Cells from 3D Tumor Spheroids. Current Protocols 2, e569. https://pubmed.ncbi.nlm.nih.gov/36286844/ 

Achyut Dahal, Pravin Parajuli, Sitanshu S. Singh, Leeza Shrestha, Jafrin Jobayer Sonju, Prajesh Shrestha, Ioulia Chatzistamou, Seetharama Jois (2022). Targeting Protein-Protein Interaction for Immunomodulation: A Sunflower Trypsin Inhibitor Analog Peptidomimetic Suppresses RA Progression in CIA model. Journal of Pharmacological Sciences 149( 3), 124-138. https://pubmed.ncbi.nlm.nih.gov/35641025/

Sitanshu S Singh , George Mattheolabakis , Xin Gu Sita Withers, Achyut Dahal, Seetharama Jois (2021). A grafted peptidomimetic for EGFR heterodimerization inhibition: Implications in NSCLC models. Eur J Med Chem. 216: 113312. https://pubmed.ncbi.nlm.nih.gov/33667849/ 

Sable, R., Durek, T., Taneja, V., Craik, D., Pallerla, S., Jois, Seetharama. (2016). Constrained Cyclic Peptides as Immunomodulatory Inhibitors of the CD2:CD58 Protein-Protein interaction. ACS Chemical Biology 11: 2366-2374. https://pubmed.ncbi.nlm.nih.gov/27337048/ 

David, L., Gokhale, A., Jois S, Johnson, A., Behrens ,M., Luthra, H., Taneja, V. (2016) CD74/DQA1 dimers predispose to the development of arthritis in humanized mice. Immunology. 147: 204-211. https://pubmed.ncbi.nlm.nih.gov/26524976/ 

Kaufman, N.E.M., Meng, Q., Griffin, K.E., Singh, S.S., Dahal, A., Zhou, Z., Fronczek, F.R., Mathis, J.M., Jois, S.D., Vicente, M.G.H. (2019). Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor. J Med Chem. 62(7):3323-3335. https://pubmed.ncbi.nlm.nih.gov/30835998/ 

Kaufman NEM, Dhingra S, Jois SD, Vicente MDGH. (2021).Molecular Targeting of Epidermal Growth Factor Receptor (EGFR)and Vascular EndothelialGrowth Factor Receptor (VEGFR). Molecules 26(4):1076. https://pubmed.ncbi.nlm.nih.gov/33670650/ 

Achyut Dahal, Jafrin Jobayer Sonju, Konstantin G. Kousoulas, Seetharama Jois (2021). Peptides and Peptidomimetics as Therapeutics for Covid-19. Peptide Science e24245. https://pubmed.ncbi.nlm.nih.gov/34901700/ 

Sable, R., Jambunathan, N., Kousoulas, K.G., Seetharama Jois. (2018). Proximity ligation assay to study protein-protein interactions of proteins on two different cells. Biotechniques. 65:149-157. https://pubmed.ncbi.nlm.nih.gov/30227746/ 

PUBMED BIBLIOGRAPHY

GOOGLE SCHOLAR CITATIONS

Grant Funding

Current

5R01CA255176 04/01/2021-03/31/2026. Project title: Molecular mechanism of EGFRs protein-protein interaction inhibition by a grafted peptide in NSCLC. Role PI: Seetharama Jois. Funding agency: NCI/NIH, Amount of award: $1,648,255. The goal of this project is to evaluate the drug-like properties of sunflower trypsin inhibitor (SFTI)-grafted peptides as possible therapeutic agents for non-small cell lung cancer treatment.

Completed

Louisiana Biomedical Research network (LBRN) Translational research award 05/01/2019-08/19/2020. Project title: Immunomodulation by plant-based grafted cycle peptides: Implication in treating chronic inflammation. Role PI: Seetharama Jois. Funding agency: LBRN, Amount of award: $56,000. The goal of this project is to modulate the signal generated by co-stimulatory molecules in autoimmune diseases using stable peptides.

1 R15 CA188225-01A1 09/01/2015-08/31/2019. Project title: Molecular mechanism of EGFR heterodimerization: inhibition by a peptidomimetic. Role PI: Seetharama Jois. Funding Agency NIH (R15 mechanism), Amount of award $394,376. The goal of this project is to evaluate the molecular mechanism of inhibition of dimerization by a peptidomimetic and to evaluate the drug-like properties of the designed molecule.

1R01CA179902-01A1 08/01/2014–07/30/2019. Title: CRC-specific near-IR agents for tumor imaging. Role: Consortium PI (PI: Graca M.H. Vicente, LSU Baton Rouge). Funding agency: Subaward: Louisiana State University. NCI/NIH, Amount of subaward: $200,204. The goal of this project is to use near-IR conjugates to fluorescently label colorectal tumor foci. by targeting of epidermal growth factor receptors (EGFR) and human carcinoembryonic antigen (CEA), both over-expressed in colon cancer cells.

LEQSF(2016-17)-ENH-TR-30 (Jois) 06/01/2016-07- 06/30/2017. Title:Establishment of Peptide and Protein Facility at ULM. Role: PI. Amount of award: $73,706.00 (total). The major goal of this project is to establish a protein/peptide facility at ULM.