Sajani Lakka, PhDSajani Lakka

Associate Professor

Contact Information
Section of Hematology/Oncology, MC 734
University of Illinois at Chicago
909 South Wolcott, Room5030
Chicago, IL 60612
Phone: (312) 996-3468
Fax: (312) 413-7963
Email: slakka@uic.edu

Areas of Interest
Brain Tumor Growth

Biography
Sajani completed her doctorate degree in Biochemistry at the Osmania University in Hyderabad, India. She worked as a post-doctoral fellow at M. D. Anderson Cancer Center in Houston and at the University of Illinois College of Medicine at Peoria and later joined as a faculty member at the college of Medicine in Peoria. Sajani has published 61 peer-reviewed publications in leading scientific journals and three textbook chapters on cancer. She has been invited to national and international meetings to present her research findings. Sajani regularly serves as a peer-reviewer for a number of jhournals and serves on the ACS grant study section.

Research Interests
Sajani's laboratory has now focused on two research directions:

1.) Exporing the molecular mechanisms wherby SPARC modulates cell fate and tumorgenesis in brain tumors
2.) Identifying the role of mir-203 in brain tumor growth and differentiation.

The main focus of my research program is to study roles of ECM components on medulloblastoma growth focusing on SPARC, a matricellular protein. SPARC is a member of matricellular proteins that plays roles in normal tissue development, cell adhesiom, migration, tumor metastasis, and angiogenesis. Studies from our lab have shown that SPARC expression is suppressed in human medulloblastoma tissues and can function as a tumor suppressor in medulloblastoma tumors. We have also discovered that SPARC is involved in the induction of autophagy and tumor cell apoptosis through a mitochondrial death pathway.  Another part of our research program focuses on the effect of SPARC on treatment efficacy with a focus on signaling and epigenetics using cellular, molecular, and biochemical approaches, and xenograft mouse models. These studies will provide important insights into mechanisms that could prevent medulloblastoma progression. 

Distinct patterns of microRNA expression have been observed in many cancers including glioblastomas, Allelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM and was thought to harbor multiple tumor suppressor genes associated with GBM.  This region encodes several microRNAs including microRNA 203 (miR-203).  We identified that miR-203 is suppressed in GBM.  We are therefore investigating the role of mir-203 expression for its clinical management.

Selected Publications

  1. Lakka, S.S., Rajan, M., Gondi, C., Yanamandra, N., Chandrasekar, N., Jasti, S., Adachi, Y., Siddique, K., Gujrati, M., Olivero, W., Dinh, D., Kouraklis, G., Kyritsis, A., and Rao, J., “Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion,” Oncogene, 21, 8011-8019, 2002.
  2. Lakka, S. S., Gondi, C., Yanamandra, N., Dinh, D., Olivero, W., Gujrati, M., and Rao, J.S. “Synergistic Downregulation of Urokinase Plasminogen Activator (uPAR) and Matrix Metalloproteinase (MMP-9) in SNB19 glioblastoma cells efficiently inhibits glioma cell invasion,” Can. Research, 63, 2454-2461, 2003.
  3. Lakka, S S., Gondi, C., Yanamandra, N., Olivero, W., Dinh, D., Gujrati, M., and Rao, J. S. “Inhibition of Cathespin B and MMP-9 gene expression in glioma cell lines via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis,” Oncogene, 23:4681-4689, 2004.
  4. Lakka, S. S. Gondi, C., Dinh, D., Olivero, W., Gujrati, M., and Rao, J.S. “Specific interference of uPAR and MMP-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas,” J Biol Chem, 280:21882-21892, 2005.
  5. Rao, J.S., Gondi, C., Chetty, C., Chittivelu, S., Joseph, P.A., and Lakka, S.S. “Inhibition of invasion, angiogenesis, tumor growth and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells,” Mol Cancer Ther 4:1399-1408, 2005.
  6. Chetty, C., Bhoopathi, P., Joseph, P., Chittivelu, S., Rao, J.S., and Lakka, S. "Adenovirus-mediated small interfering RNA against matrix metalloproteinase-2 suppresses tumor growth and lung metastasis in mice, Molecular Cancer Therapeutics, 5:2289-2299, 2006.
  7. Rao, J.S., Bhoopathi, P., Chetty, C., Gujrati, M., Lakka, S.S. “MMP-9 siRNA induced senescence resulting in inhibition of medulloblastoma growth via p16INK4A and MAPK Pathway,” Cancer Research, 67:4956-4964, 2007.
  8. Bhoopathi, P., Chetty, C., Kunigal, S., Vanamala, S., Rao, J.S., Lakka, S.S. “Blockade of tumor growth due to MMP 9 inhibition is mediated by sequential activation of β1 integrin, ERK and NKκB,” J. Biol. Chem. 283:1545-1552, 2008. PMCID 2206181.
  9. Lakka, S.S. and Rao, J.S. “Antiangiogenic therapy in brain tumors,” Expert Rev. of Neurotherapeutics, 8:1457-1473, 2008. PMCID 2656359.
  10. Chetty, C., Bhoopathi, P., Rao, J.S., Lakka, S.S. “Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells,” Int. J. Cancer, 124:2468-2477, 2009. PMCID 2663016.
  11. Bhoopathi, P., Chetty, C., Gujrati, M., Dinh, D.H., Rao, J.S., Lakka, S.S. “The role of MMP-9 in the anti-angiogenic effect of secreted protein acidic and rich in cysteine,” British J. Cancer, 102:530-540, 2010. PMCID 2822952.
  12. Bhoopathi P, Chetty C, Gujrati M, Dinh DH, Rao JS, Lakka S.S." Cathepsin B facilitates autophagy-mediated apoptosis in SPARC over expressed primitive neuroectodermal tumor cells. Cell Death Differ. 2010 Oct;17(10):1529-39. PMID: 20339379.
  13. Bhoopathi, P., Chetty, C., Ranadheer Dontula, Meena Gujrati, Dzung H. Dinh, Jasti S. Rao, and Lakka. S.S "SPARC Stimulates Neuronal Differentiation of Medulloblastoma Cells via the Notch1/STAT3 Pathway". Cancer Res; 71(14); 1–12. 2011. PMID 21613407.
  14. Chetty C, Rao J.S. and Lakka. S.S Pharmacogenomics 12(4):535-46 (2011) PMID 21521025.
  15. Praveen Bhoopathi, Christopher S. Gondi, Meena Gujrati, Dzung H. Dinh and Lakka S.S. "SPARC mediates Src-induced disruption of actin cytoskeleton via inactivation of small GTPases Rho–Rac–Cdc42" Cellular Signaling (2011). PMID: 21798346