JAGGI, MEENA

Associate Professor
Pharmaceutical Sciences

Office: 226 Cancer Research Building
Tel: (901) 448-5600
mjaggi@uthsc.edu

Education

  • Ph.D., Central Drug Research Institute, Cell Biology/Reproductive Endocrinology

Research Interest/Specialty

Kinase, molecular therapeutics, cancer biology, drug delivery and nanotechnology

Research Keywords

PKD1, beta-catenin, E-cadherin, Kinase, MUC 13

Research Description

The primary focus of my research is to identify and evaluate the functional significance of cell-cell adhesion molecules known as cadherins and catenins in cancer progression and to understand the regulation of cadherin/catenin complex activity by Protein Kinase D signaling. In-depth knowledge of molecular mechanisms involved in signal transduction of human cancers is critical for the development of biomarker for early detection of cancer and rationalized structure-based drug designing. We have identified a novel interaction between E-cadherin/ß-catenin complex and Protein Kinase D1 (PKD1), an important modulator of several kinase signal-transduction pathways in benign and malignant human diseases. Downstream signaling of the E-cadherin/ ß-catenin and PKD1 interaction alters malignant phenotype of cancer cells.

The cadherins are members of a large family of transmembrane glycoproteins that mediate calcium dependent homotypic adhesion and require association with the actin cytoskleton through cytoplasmic proteins called catenins. The cadherin family of proteins is implicated in cell sorting during normal development. Aberrant expressions of cadherins and catenins have been implicated in the carcinogenesis and invasiveness of tumor cells. Malignant transformation is often characterized by major changes in the organization of the cytoskeleton, decreased cell-cell adhesion, and aberrant adhesion-mediated signaling. Disruption of normal cell-cell adhesion in transformed cells contributes to enhanced tumor cell migration and proliferation, which leads to invasion and metastasis. This disruption can be achieved by down-regulating the expression of cadherin or catenin family members or by activation of signaling pathways that prevent the assembly of junctions. We are attempting to understand how the activity the cadherin/catenin complex is regulated.

PKD1 is a serine/threonine-specific kinase that performs a variety of functions in cells and is target-dependent. PKD1 has been shown to play a major role in a multitude of cellular functions including apoptosis, immune response, DNA synthesis, cell proliferation and invasion, Golgi trafficking and intracellular signal transduction. I have identified a novel interaction between E-cadherin and PKD1 that results in E-cadherin phosphorylation. Downstream signaling of the interaction alters cellular aggregation and motility of cancer cells. I have also shown down-regulation of PKD1 and aberrant expression of E-cadherin, N-cadherin and ß-catenin in human prostate cancer progression in three publications. ß-catenin, a distinct member of the cadherin-catenin protein complex that plays a dual role in cell adhesion as well as in Wnt (Wingless type) signaling pathway associated with cell proliferation. In addition, we will also study the ß-catenin subcellular modulation by the PKD1 and regulation of membrane trafficking of ß-catenin by PKD1.

Information for the Lay Person   Tab Page:

The primary focus of my research is to identify and evaluate the functional significance of cell-cell adhesion molecules known as cadherins, catenins in normal development and cancer progression. Our research is also aimed to understand the regulation of cadherin/catenin complex activity by Protein Kinase D signaling. In addition we are in process of investing how MUC13 mucin plays a role in abruption of cell-cell adhesion assembly in cancer cells. In-depth knowledge of molecular mechanisms involved in signal transduction of human cancers is critical for development of biomarker for early detection of cancer and rational and structure-based drug designing.

Publications

  1. Yallapu, MM, Katti, KS, Katti, DR, Mishra, SR, Khan, S, Jaggi, M, Chauhan, SC. The roles of cellular nanomechanics in cancer. Med Res Rev, 35 (1), 198-223, 2015.
  2. Maher, DM, Khan, S, Nordquist, JL, Ebeling, MC, Bauer, NA, Kopel, L, Singh, MM, Halaweish, F, Bell, MC, Jaggi, M, Chauhan, SC. Ormeloxifene efficiently inhibits ovarian cancer growth. Cancer Lett, 356 (2 Pt B), 606-12, 2015.
  3. Khan, S, Ebeling, MC, Zaman, MS, Sikander, M, Yallapu, MM, Chauhan, N, Yacoubian, AM, Behrman, SW, Zafar, N, Kumar, D, Thompson, PA, Jaggi, M, Chauhan, SC. MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. Oncotarget, 5 (17), 7599-609, 2014.
  4. Gara, RK, Kumari, S, Ganju, A, Yallapu, MM, Jaggi, M, Chauhan, SC. Slit/Robo pathway: a promising therapeutic target for cancer. Drug Discov Today, 2014.
  5. Sundram, V, Ganju, A, Hughes, JE, Khan, S, Chauhan, SC, Jaggi, M. Protein kinase D1 attenuates tumorigenesis in colon cancer by modulating β-catenin/T cell factor activity. Oncotarget, 5 (16), 6867-84, 2014.
  6. Yallapu, MM, Khan, S, Maher, DM, Ebeling, MC, Sundram, V, Chauhan, N, Ganju, A, Balakrishna, S, Gupta, BK, Zafar, N, Jaggi, M, Chauhan, SC. Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials, 2014.
  7. Ganju, A, Yallapu, MM, Khan, S, Behrman, SW, Chauhan, SC, Jaggi, M. Nanoways to overcome docetaxel resistance in prostate cancer. Drug Resist Updat, 17 (1-2), 13-23, 2014.
  8. Khan, S, Ansarullah, , Kumar, D, Jaggi, M, Chauhan, SC. Targeting microRNAs in pancreatic cancer: microplayers in the big game. Cancer Res, 73 (22), 6541-7, 2013.
  9. Gupta, BK, Maher, DM, Ebeling, MC, Stephenson, PD, Puumala, SE, Koch, MR, Aburatani, H, Jaggi, M, Chauhan, SC. Functions and regulation of MUC13 mucin in colon cancer cells. J Gastroenterol, 2013.
  10. Yallapu, MM, Ebeling, MC, Khan, S, Sundram, V, Chauhan, N, Gupta, BK, Puumala, SE, Jaggi, M, Chauhan, SC. Novel curcumin-loaded magnetic nanoparticles for pancreatic cancer treatment. Mol Cancer Ther, 12 (8), 1471-80, 2013.
  11. Yallapu, MM, Ebeling, MC, Jaggi, M, Chauhan, SC. Plasma proteins interaction with curcumin nanoparticles: implications in cancer therapeutics. Curr Drug Metab, 14 (4), 504-15, 2013.
  12. Gara, RK, Sundram, V, Chauhan, SC, Jaggi, M. Anti-cancer potential of a novel SERM ormeloxifene. Curr Med Chem, 20 (33), 4177-84, 2013.
  13. Gupta, BK, Maher, DM, Ebeling, MC, Sundram, V, Koch, MD, Lynch, DW, Bohlmeyer, T, Watanabe, A, Aburatani, H, Puumala, SE, Jaggi, M, Chauhan, SC. Increased expression and aberrant localization of mucin 13 in metastatic colon cancer. J Histochem Cytochem, 60 (11), 822-31, 2012.
  14. Zaman, MS, Maher, DM, Khan, S, Jaggi, M, Chauhan, SC. Current status and implications of microRNAs in ovarian cancer diagnosis and therapy. J Ovarian Res, 5 (1), 44, 2012.
  15. Yallapu, MM, Jaggi, M, Chauhan, SC. Curcumin nanomedicine: a road to cancer therapeutics. Curr Pharm Des, 19 (11), 1994-2010, 2012.
  16. Yallapu, MM, Othman, SF, Curtis, ET, Bauer, NA, Chauhan, N, Kumar, D, Jaggi, M, Chauhan, SC. Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications. Int J Nanomedicine, 7, 1761-79, 2012.
  17. Yallapu, MM, Jaggi, M, Chauhan, SC. Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today, 17 (1-2), 71-80, 2012.
  18. Chauhan, SC, Ebeling, MC, Maher, DM, Koch, MD, Watanabe, A, Aburatani, H, Lio, Y, Jaggi, M. MUC13 mucin augments pancreatic tumorigenesis. Mol Cancer Ther, 11 (1), 24-33, 2012.
  19. Yallapu, MM, Dobberpuhl, MR, Maher, DM, Jaggi, M, Chauhan, SC. Design of curcumin loaded cellulose nanoparticles for prostate cancer. Curr Drug Metab, 13 (1), 120-8, 2012.
  20. Yallapu, MM, Ebeling, MC, Chauhan, N, Jaggi, M, Chauhan, SC. Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes. Int J Nanomedicine, 6, 2779-90, 2011.
  21. Sundram, V, Chauhan, SC, Ebeling, M, Jaggi, M. Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS One, 7 (4), e35368, 2011.
  22. Sundram, V, Chauhan, SC, Jaggi, M. Emerging roles of protein kinase D1 in cancer. Mol Cancer Res, 9 (8), 985-96, 2011.
  23. Yallapu, MM, Jaggi, M, Chauhan, SC. Design and engineering of nanogels for cancer treatment. Drug Discov Today, 16 (9-10), 457-63, 2011.
  24. Maher, DM, Gupta, BK, Nagata, S, Jaggi, M, Chauhan, SC. Mucin 13: structure, function, and potential roles in cancer pathogenesis. Mol Cancer Res, 9 (5), 531-7, 2011.
  25. Yallapu, MM, Othman, SF, Curtis, ET, Gupta, BK, Jaggi, M, Chauhan, SC. Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy. Biomaterials, 32 (7), 1890-905, 2011.