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Dr. Jayshree Mishra's Lab

Research Goals

The Mishra lab focuses on two areas:

  1. Target identification in drug discovery
  2. Developing novel biomarkers for early detection of childhood obesity and colon cancer.

Identifying therapeutic target for gastrointestinal complications:
We are broadly interested in understanding the post translational modification of the drug transporter on the intestinal epithelial cells and how these proteins regulate under normal and diseased states. Through our study we have identified drug transporter proteins (DTP) in the mechanisms of mucosal inflammation as it related to pharmacokinetic and pharmacodynamical disposition of oral medications and obesity. Though several DTPs are expressed in the mucosal epithelial surfaces, there is no report on the epithelial specific transcriptional and translational regulations of key efflux functions mediated by these transporters. To our surprise, we found that key target proteins are tyrosine phosphorylated at key residues through posttranslational modification by previously unknown enzymes. So far, we have published our initial findings and are in the process of expanding the research through securing external funding

Biomarker discovery:
Our lab explores on developing (a) a novel non-invasive biomarker for the early detection of childhood obesity. As childhood obesity is quite prevalent in the South Texas where our goal is to develop a non-invasive early predicator of oral microbiome-based biomarker for childhood obesity to track the onset and progression of obesity in the pediatric population. This study was funded from Vishal Raju Bhagat Foundation since 2018. This is an ongoing project and expected to not only provide the preliminary data for subsequent significant funding but also give an insight information on the significance of the associations between oral microbiome and inflammation in rapid weight gain in children from ages 0-5yrs in our community. In future, our goal is to identify the specific group of pathobiont responsible for the inflammation associated obesity with an aim to develop tailored therapeutic interventions. (b) a  novel semi-invasive biomarker for an early detection of colorectal cancer. Conventional screening methods have several limitations including late-stage detection and post-detection patient survival, Currently, there is no screening procedure available to detect CRC at a very early stage. Based on our sub molecular understanding of intestinal restitution (Mishra etal JBC 2017), we have developed a probe and associated diagnostic kit that does prognosis of CRC at the pre-polyp stage, way earlier than any colonoscopy can pick-up. Our technology is based on epithelial mesenchymal transition that uses the mechanism that facilitates the transition of colonic epithelial cells from proliferative stage to a differentiated (non-proliferative) stage. This probe can not only play an important role in the early detection and treatment of patients with colorectal cancer but also increase life expectancy post detection. This project was awarded from Texas A&M PESCA grant in 2019, and now we have enough preliminary data to submit NIH grant.

Lab Funding

  • NIH-SBIR-GM109528 Kumar (PI) Mishra (Co-I); Development of a novel ELISA kit for screening potential JAK3 inhibitors. 06/2014-06/2016
  • TAMU-PESCA Mishra (PI: Mishra); Development of a novel biomarker for the early detection of colon cancer 06/2019- 07/2022
  • Vishal Raju Bhagat Foundation (PI: Mishra): Development of an oral microbiome based novel biomarker for the early detection of childhood obesity. 07/2018- 12/2020

Patents

  • Kumar N, and Mishra J. A Novel High Throughput Assay for finding new Jak3 Interacting Compounds, Biomolecules, and Inhibitors. US Non-Provisional patent number US 14/483,622; US20150344934 A1. (Under negotiation for licensing).
  • Kumar N, and Mishra J. Methods of Screening for Janus Kinase 3 Interacting Compounds. United States Patent. Patent No.: US 9,739,779. Date of award: Aug 22, 2017.
  • Kumar N, and Mishra J. Biomarkers for Early Detection of Colorectal Cancer. TAMU-HSC. No.: 4812HSC18. Date: September 11, 2017

Publications

  • Narendra Kumar1, Salim Surani, George Udeani, Sara Mathew, Sharon John, Soniya Sajan, Jayshree Mishra. Drug-Induced Liver Injury and prospect of Cytokine Therapy; A focus on IL-2 based therapies, Life Sciences (May 2021) 1;278: 119544.doi: 10.1016/j.lfs.2021.119544. Epub 2021 May 1.
  • Narendra Kumar, Longxiang Kuang Ryan Villa, Priyam Kumar, Jayshree Mishra, Mucosal Epithelial Jak Kinases in Health and Diseases. Mediators of inflammation (March 2021). 2021 Mar 16; 2021:6618924. doi: 10.1155/2021/6618924.
  • Jayshree Mishra and Narendra Kumar Intestinal (BCRP) for Drug Efflux and Barrier Functions in Obesity, Medicine Innovates, 2020, volume: Mechanism of action.
  • Jayshree Mishra and Narendra Kumar; Intestinal Breast Cancer Resistance Protein (BCRP) Requires Janus Kinase 3 Activity for Drug Efflux and Barrier Functions in Obesity. J Biol Chem 2019 Nov 29; 294(48):18337-18348
  • Jayshree Mishra, Jugal Kishore Das and Narendra Kumar; Janus Kinase 3 phosphorylation of βcatenin NTD regulates adherence junction J Biol Chem 2017. Oct 6; 292(40):16406-16419.PMID: 28821617
  • Jayshree Mishra, Raj K Verma, and Narendra Kumar. Role of Janus Kinase 3 in Predisposition to Obesity and Metabolic Syndrome J Biol Chem. 2015; 289(23):15951-6
  • Jayshree Mishra and N. Kumar. Adapter protein Shc regulates Janus kinase 3 phosphorylation. J Biol Chem. (Accelerated Publication) 2014; 289(23):15951-6
  • Jayshree Mishra, Karanki S Kumar N, Identification of molecular switch regulating Interaction of Janus Kinase 3 with cytoskeletal proteins J Biol Chem. (Accelerated publication) 2012; 287(49):41386- 91).
  • Jayshree Mishra, J Dromund, SH Quazi, SS Karanki, JJ Shaw, B Chen, N Kumar. Prospective of colon cancer treatments and scope for combinatorial approach for enhanced cancer cell apoptosis. Crit Rev Oncol Hematol. 2012. doi:pii: S1040-8428(12)00197-7.
  • N Kumar, Jayshree Mishra, Sohel Quazi. Training the defense system for modern-day warfare: the horizons for immune-related cancer treatment and vaccines for cancer (2012) J immunodefic Disord. 2012; 1(2). P. ii:1000e106.
  • Jayshree Mishra, C Water, N Kumar. Molecular mechanism of interleukin-2 induced mucosal homeostasis. Am J Physiol Cell Physiol. 2012; 302(5):C735-47.
  • Jayshree Mishra, ZQ, B Neudeck. Activation of TLR-4 receptor increases cell surface P-glycoprotein expression with decreased activity, Drug Metabolism and Disposition. 2008; 36(10):2145-9.
  • N Kumar, Jayshree Mishra, VS Narang, CM Waters. Janus Kinase 3 (Jak3) regulates interleukin induced mucosal wound repair through tyrosine phosphorylation of villin. J Biol Chem., (Accelerated publication) 2007;282(42), 30341-5.

Lab Members

Mimansha J Shah

Shah J Mimansha
Student Research Assistant