Komaraiah Palle, Ph.D.
Department of Cell Biology and Biochemistry
Texas Tech University Health Sciences Center
3601 4th Street, Lubbock, TX 79430-6540
Office Phone: (806) 743-2703
Research in our laboratory is focused on understanding the molecular mechanisms of carcinogenesis processes and develop preventive and therapeutic interventions for different malignant and other diseases by basic and translational research. Thus, the focus our research group is two dimensional: 1) The basic science research projects focused on understanding the complex interplay between tumor suppressors and oncogenes in genome maintenance, and the mutations or their deregulation in carcinogenesis and tumor development. Primarily, DNA damage response and repair signaling genes are tumor suppressors that constantly protect chromosomal DNA from environmental and metabolically generated genotoxins, including oncogenic replication stress. Mutations in these genes cause genome instability/cancer predisposition syndromes such as Fanconi anemia (FA) and Breast and Ovarian Cancer early onset (BRCA). In contrast, tumor cells also acquire resistance to chemo and radiation therapy by altered regulation of cell cycle checkpoints (ATM, ATR) and DNA repair networks. These mechanisms and their regulation are highly complex, and often they are differentially regulated during organism development and in tumor cells, particularly in the context of oncogenic or growth factor signals they adopt. Our research employs multidisciplinary approaches to identify gene regulatory networks and cell signaling mechanisms that control these processes.
2) The translational research projects focused on genetic and epigenetic mechanisms that tumor cells adopt to survive from oncogenic replication stress and from chemo and radiation therapy. My lab is particularly interested in understanding how activated oncogenic signals (growth factor receptors, signaling proteins such as Hedgehog/GLI, RAS, inflammatory and epigenetic regulators) influence DNA repair and cell cycle checkpoint signaling cascades. Our goal is to identify key regulators of these complex networks in tumors cells and develop rotationally designed therapeutic combinations to effectively kill tumor cells, which are also known as proof-of-concept based synthetic lethality approaches. Areas of my translational interests are primarily Ovarian and Breast cancers, and extended to other malignancies.
- Synthetic lethality approaches to treat ovarian and breast cancers
- Ubiquitin signaling in epigenetic reprogramming (Cancer Stem Cell phenotype) of tumor metabolism and therapeutic relapse: Development of novel small molecule inhibitors for RAD6 to treat relapsed cancers
- Rad18/Rad6- mediated ubiquitin signaling in regulation of FA-BRCA tumor suppressor pathway and its influence on chemo and radiation resistance
- Hedgehog/Gli1 signaling mediated regulation of DDR and repair genes during carcinogenesis and chemoresistance: Development of rationally designed therapeutic combinations
- Novel functions and regulation of FANCJ/BRIP1 in response to DNA damage and during other biological processes.
- Role and regulation of PACS-1 during development and disease
- Oxidative stress and altered estrogen metabolism in cancer, neurological disorders and other diseases
- Mani C, Pai S, Papke CM, Palle K* and Gmeiner WH*. (2018) Thymineless Death by the Fluoropyrimidine Polymer F10 Involves Replication Fork Collapse and is Enhanced by Chk1 Inhibition. Neoplasia. 20 (12):1236-1245. (* Co-corresponding authors)
- Somasagara RR#, Spencer SM#, Tripathi K, Clark DW, Mani C, Madeira da Silva L, Scalici J, Kothayer H, Westwell AD, RocconiRP, Palle K. (2017) RAD6 promotes DNA repair and stem cell signaling in ovarian cancer and is a promising therapeutic target to prevent and treat acquired chemoresistance. Oncogene 30;36(48):6680-6690. PMID: 28806395; PMCID: PMC5709226 Research Comment highlighted in: Transl Cancer Res 2017;6(Suppl 9):S1476-S1479
- Ananthapur V, Clark DW, Nallari P, Cingeetham V, Thangaraj K, Alla GR, Akka J, Malladi VK, Ramaiyer RR and Palle K (2017) Mutation analysis of FANCJ/BRIP1 in a family with history of male and female breast cancer in India: a case study. J Brest Can 20(1):104-107.
- Tripathi K, Mani C, Somasagara RR, Clark DW, Ananthapur V, Vinaya K, Palle K. (2017) Detection and evaluation of estrogen DNA-adducts and their carcinogenic effects in cultured human cells using biotinylated estradiol. Molecular Carcinogenesis. 56(3):1010-1020.
- Kothayer H, Spencer S, Tripathi K, Westwell AD and Palle K (2016) Synthesis and in vitro anticancer evaluation of some 4,6-diamino1,3,5triazine-2-carbohydrazides as Rad6 Ubiquitin conjugating enzyme inhibitors. Bioorganic and Medicinal Chemistry Letters 26(8):2030-4.
- Tripathi K, Mani C, Clark D, Barnett R, Palle K (2016) Rad18 is required for functional interactions between FANCD2, BRCA2, and Rad51 to repair DNA topoisomerase 1-poisons induced lesions and promote fork recovery. Oncotarget. 7(11):12537-53.
- Rani V, Deep G, Singh RK and Palle K, Yadav UCS (2016) Oxidative Stress in Metabolic Disorders: Pathogenesis, Prevention, and Therapeutics. Life Sciences. S0024-3205(16)30052-2; PMID: 26851532 (Invited review).
- Clark DW, Tripathi K, Dorsman JC and Palle K (2015) FANCJ deficiency compromises the stability of FANCD2/FANCI complex and promotes their degradation in a Caspase-3 mediated mechanism. Oncotarget, 6 (30); 28816-32.
- Palle K*, Mani C, Tripathi K and Athar M. (2015) Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance. Cancers, 7, 2330-2352.
- Tripathi K, Mani C, Barnett R, Nalluri S, Bachaboina L, Rocconi RP, Athar A, Owen LB, Palle K (2014) Gli1 regulates S-phase checkpoint in tumor cells via Bid and its inhibition sensitizes them to DNA topoisomerase 1 inhibitors. Journal of Biological Chemistry 289(45):31513-25.
- Meng E, Mitra A, Tripathi K, Finan MA, Scalici J, McClellan S, Reed E, Shevde LA, Palle K*, Rocconi RP * (2014). ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling, PLoS One 9(9):e107142. (* Co-corresponding authors).
- Palle K*, Vaziri C (2011). Rad18-mediated activation of fanconi anemia pathway in response to Top1 inhibitor camptothecin. Cell Cycle 10(10): 1625-38; PMID: 21478670; PMCID: PMC3127162 (*corresponding author). Selected for featuring in News and Views. Written by Dr. Anindya Dutta (University of Virginia) and Dr. Satoshi Tateishi (Kumamoto University, Japan.
- Day T, Palle K, Barkley LR, Yoshizawa-Sugata N, Zou Y, Tateishi S, Verreault A, Masai H, Vaziri C. (2010) Cdc7-mediated posphorylation of Rad18 directs the accumulation of DNA polymerase eta at sites of stalled replication. Journal of Cell Biology 191(5):953-66
- Song IY*, Palle K*, Gurkar A, Tateishi S, Kupfer GM and Vaziri C (2010) Rad18-mediated trans-lesion synthesis of bulky DNA adducts is coupled to activation of the fanconi anemia DNA repair pathway. Journal of Biological Chemistry 285:31525-36; PMID: 20675655; PMCID: PMC2951227 (*contributed equally).
- Palle K, Pattarello L, van der Merwe M, Benedetti P, Bjornsti M-A (2008) Disulfide crosslinks reveal conserved features of DNA topoisomerase I architecture and a role for the N-terminus in clamp closure. Journal of Biological Chemistry 283: 27767-75
- Koster DA, Palle K, Bot ESM, Bjornsti M-A, Dekker NH (2007) “Antitumor drugs impede DNA uncoiling by Topoisomerase I”, Nature 448: 213-7 (with cover illustration) and Research comment highlighted, Nature Structural & Molecular Biology 14:688, 2007). Featured in Nature Podcasts and many national and international news.