Madhavi P. Kadakia, PhD
Ph.D.: University of Pittsburgh (1995)
Postdoctoral: Pittsburgh Cancer Institute (1995–1998)
The Cancer Institute of New Jersey (1998–1999)
My laboratory is focused on deciphering the signaling pathways regulated by p63 and its role in cancer and development. p63 is a member of the p53 family member and has been shown to play a role in tumorigenesis, maintenance of epithelial stem cells and development. p63 has a complex genomic organization that results from alternate promoter usage and alternative splicing and is a homolog of the tumor suppressor protein p53. Unlike the p53 knockout mice which exhibit a high incidence of spontaneous tumors, the p63 knockout mice displays severe developmental abnormalities including limb truncations and craniofacial abnormalities. p63 mutations are also observed in various human developmental syndromes.
Our laboratory has been involved in understanding the signaling pathways regulated by p63 to better understand the role of p63 in development as well as cancer. We have studied the effects of naturally occurring mutant forms of p63 on the biological activity of p53 and p63 and shown that the mutant p63 differentially regulates known p53 and p63 target genes and could explain the difference in the biology of two members of the p53 family, p53 and p63. We have shown that p63 regulates sonic hedgehog, known to be important in both development and cancer. Recently we demonstrated that ΔNp63α, the most abundant and physiologically relevant p63 isoform, negatively regulates PTEN, a tumor suppressor gene often deregulated in a variety of cancer including the model system we focus on in my laboratory, skin cancer. Our studies on examining the role of p63 in cancer progression demonstrated that vitamin D receptor (VDR) is regulated by p63 and p73, another member of the p53 family and its biological significance. Currently studies in my laboratory are focused on examining the mechanism behind feedback regulation of p63 by VDR and VD3.These studies will address the discrepancy whether VD3 inhibits or promotes cell survival and provide further insight into its use as a chemotherapeutic adjuvant for anti-cancer therapy and fill the gap in the understanding of VD3 mediated regulation of ΔNp63α levels and its role in the development and progression of non melanoma skin cancer.
Recently my laboratory has been involved in examining the differential expression of known microRNAs and unknown small RNAs in tissue and plasma sample of patients with Barrett’s esophagus (BE), Esophageal adenocarcinoma (EAC) in order to identify circulating microRNA biomarkers for early detection of EAC using next generation sequencing. My laboratory has recently received funding to obtain next generation sequencer along with the top of the line Real time PCR machine with high throughput capabilities to facilitate these studies.
Kadakia Lab 2015
- Hill NT, Zhang J. Leonard MK, Lee M, Shamma HN, Kadakia MP*. 1a- 25 Dihydroxyvitamin D3 and the vitamin D receptor regulates DNp63a levels and cell proliferation. 2015. Cell Death Dis 6:e1781. doi: 10.1038/cddis.
- Hill NT, Gracia-Maldonado GH, Leonard MK, Harper AR, Tober KL, Oberyszyn TM, Kadakia MP*. Role of Vitamin D3 in Modulation of DNp63a Expression during UVB induced Tumor Formation in SKH-1 mice. 2014. PLoS One. 9(9):e107052.
- Lehman JA, Hauck, PM, Gendron JM, Batuello CN, Eitel JA, Albig A, Kadakia MP, Mayo LD. Serdemetan Antagonizes the Mdm2-HIF1a Axis Leading to Decreased Levels of Glycolytic Enzymes. 2013. PLOS One. 8(9): e74741.
- Leonard MK, Hill NT, Bubulya PA, Kadakia MP*. The PTEN-AKt pathway impacts the integrity and composition of mitotic centrosomes. 2013. Cell Cycle. 12(9): 1406-15.
- Leonard MK, Hill NT, Grant ED, Kadakia MP*. ΔNp63α represses nuclear translocation of PTEN by inhibition of Nedd4-1 in keratinocytes. 2013. Arch Dermatol Res. Apr 16 (Epub ahead of print).
- Singh AP, Arora S, Bhardwaj A, Srivastava SK, Kadakia MP, Wang B, Grizzle WE, Owen LB, Singh S. CXCL12/CXCR4 Protein Signaling Axis Induces Sonic Hedgehog Expression in Pancreatic Cancer Cells via Extracellular Regulated Kinase- and Akt Kinase-mediated Activation of Nuclear Factor κB: Implications for Bidirectional Tumor-Stromal Interactions. 2012. J. Biol. Chem. 287: 39115-24.
- Chen J, Yang J, Chen S, Jameson J, Swope VB, Cheng T, Kadakia MP , Abdel-Malek Z, Kadekaro AL.a-Melanocyte Stimulating Hormone Suppresses Oxidative Stress Through a p53-Mediated Signaling Pathway in Human Melanocytes. 2012. Mol. Can. Res. 10: 778-786.
- Kadakia MP*, de-Fromentol CC, and Sabapathy K. The 5th International p63/p73 workshop: much more than just tumor suppression. 2012. Cell Death Differ 19(3): 549-50.
- Leonard MK, Kommagani R, Payal V, Mayo LD, Shamma HN and Kadakia MP*. ΔNp63α regulates keratinocyte proliferation by controlling PTEN expression and localization. 2011. Cell Death Differ 18(12):1924-33.
- Vaiana CA, Leonard MK, Drummy LF, Singh KM, Bubulya A, Vaia RA, Naik RR, Kadakia MP*. Epidermal Growth Factor-Layered Silicate Nanocomposites for Tissue Regeneration. 2011. Biomacromolecules.12(9):3139-46
- Lehman JA, Waning DL, Batuello CN, Cipriano R, Kadakia MP, Mayo LD. Induction of apoptotic genes by a p73-PTEN complex in response to genotoxic stress. 2011. J Bio. Chem. 286(42):36631-40
- Mieszawska AJ, Llamas JG, Vaiana CA, Kadakia MP, Naik RR, Kaplan DL. Clay enriched silk biomaterials for bone formation. 2011. Acta Biomater. Apr 22. 7(8): 3036-41.
- Sharma A, Markey M, Torres-Munoz K, Shah-Varia S, Kadakia MP, Bubulya A, Bubulya PA. Son Maintains Accurate Splicing for a Subset of Human Pre-mRNAs. 2011. J. Cell Sci. 124 (24):4286-98.
- Basu S and Kadakia MP*. The 4th International p63/p73 workshop: p53’s (older) sisters take center stage. 2010. Cell Death Differ.17(3): 562-564.
- Kommagani R, Whitlatch A. Leonard MK, Kadakia MP*. p73 is essential for vitamin D mediated osteoblastic differentiation. 2010. Cell Death Differ. 17(3): 398-407.
- Kommagani R, Leonard MK, Lewis S. Romano RA, Sinha S, Kadakia MP*. Regulation of VDR by ΔNp63α is associated with inhibition of cell invasion. 2009. J cell Sci. 122(16): 2828-35.
- Khokhar, SK., Kommagani, R., & Kadakia, MP.* Differential effects of p63 mutants on transactivation of p53 and/or p63 responsive genes. 2008. Cell Res. 18(10):1061-73.
- Kommagani, R., Payal, V., & Kadakia, MP.* Differential regulation of Vitamin D Receptor by the p53 family: p73 Dependent Induction of VDR upon DNA Damage.2007. J. Biol. Chem. 282 (41), 29847-29854.
- Paull, DE, Kelley, K, Moezzi, J, Kadakia, MP, & Berberich, SJ. Gene Expression Profiles from Needle Biopsies of Non-Small Cell Lung Carcinomas Provide Useful Signatures of the Primary Tumor. 2007.Biomarker Insights 2:253-259.
- Gupta MK, Khokhar SK, Phillips DM, Sowards LA, Drummy LF, Kadakia MP*, & Naik RR. Patterned Silk Films Cast from Ionic Liquid Solubilized Fibroin as Scaffolds for Cell Growth 2007. Langmuir 23:1315-9.
- Caserta TM, Kommagani R., Yuan Z., Robbins DJ, Mercer CA, & Kadakia MP*. p63Overexpression induces the expression of Sonic Hedgehog. 2006, Mol. Can. Res. 4:759-68.
- Heminger K., Jain V., Kadakia MP, Dwarakanath B., & Berberich SJ. Altered Gene Expression Induced by Ionizing Radiation and Glycol tic Inhibitor 2-Deoxy-Glucose in a Human Glioma Cell Line: Implications for Radio Sensitization.2006. Cancer Biol Ther.5:815-23.
- Kommagani R., Caserta TM, Kadakia MP.* Identification of vitamin D receptor as a target of p63. 2006. Oncogene25:3745-51.
- Rozenzhak SM, Kadakia MP, Caserta TM, Westbrook TR, Stone MO, & Naik RR. Cellular internalization and targeting of semiconductor quantum dots.2005. Chem Commun. 7:2217-9.
- Kadakia MP, Brown TL, McGorry M, & Berberich SJ. MdmX inhibits Smad transactivation. 2002. Oncogene21:8776-85.
- Kadakia MP, Slader C, & Berberich SJ. Regulation of p63 function of Mdm2 and MdmX. 2000. DNA Cell Biol.20(6):321-330
- Goydos J & Kadakia MP. The Clinical Relevance of the Fas-FasL Interaction. 1999. Cancer Therapeutics.2:107-112.
- Goydos J, Kadakia MP, Tirabassi MV, Perez D, & White E. Rendering Cells Resistant to Fas Ligand-Induced Apoptosis. 1999. Surgical Forum.50: 341-342
- Goydos J, Kadakia MP, Tirabassi MV, Doshi M, Perez D, & White E. Rendering Immune Effector Cells Resistant to Fas Ligand-Induced Apoptosis. 1999. J. Surg. Res. 86:275
- Kadakia MP*. Human Herpesvirus 6 Infection and Associated Pathogenesis Following Bone Marrow Transplantation. 1998. Leukemia and Lymphoma 31: 251-266.
- Kadakia MP*, Rybka WB, Stewart JA, Patton JL, Stamey FR, Elsawy M, Pellett PE, & Armstrong JA. Human Herpesvirus 6: Infection and Disease Following Autologous and Allogeneic Bone Marrow Transplantation. 1996. Blood 87: 5341-5354.
2010 Faculty Mentor Award
Boonshoft School of Medicine, Wright State University
2011 Visiting Research Scholar Fellowship
Nottingham Trent University, United Kingdom
2011 Visiting scientist
Medical Research Council, Leicester, United Kingdom
2011 Organizing committee member
5th International p63/p73 workshop, Lyon, France 2011
2013 Organizing committee member
6th International p63/p73 workshop, Chiba, Japan 2013
Active Research Grant Awards
NIH/NCI, RO1 award, P.I.
4/1/12 – 3/31/17 — “Role of ΔNp63α in vitamin D mediated cell survival in skin cancer”
Department University Research Instrumentation Program (DURIP), P.I.
7/1/2013 – 6/30/2014 — “Genomic Tools for Identification and Characterization of Biorecognition Elements for Human Performance Monitoring”