|Department:||Experimental and Systems Pharmacology|
Circadian rythm, chronopharmacology and reproductive hormones
The long term of goal of the Gaddameedhi lab is to under on how the sleep influence on cancer development and on the effectiveness of circadian clock on anti-cancer treatment. Every cell in the body has a circadian clock that regulates the cellular processes including the sleep, physiology and behavior of an organism. Recent findings on mouse models suggest that the expression of as many as 43% of protein coding genes are regulated by the circadian clock at the transcriptional level. Gaddameedhi lab is studying whether maintaining a healthy sleep schedule will increase genomic stability and decrease the gene mutations caused by ultraviolet radiation from the sun and can lead to melanoma, the deadliest form of skin cancer.
Using chronopharmacological strategies, his laboratory is also studying whether anti-cancer treatments like radiation and chemotherapy can be more effective by administering them during certain cycles of circadian rhythms because the circadian clock regulates the genotoxic mediated signaling pathways including the DNA repair, checkpoint activity, and the apoptosis.
Gaddameedhi S*, Selby CP, Kemp MG, Ye R, and Sancar A* (2014): The Circadian Clock ControlsSunburn Apoptosis and Erythema in Mouse Skin, Journal of Investigative Dermatology (epub ahead of Print), *Corresponding authors
Sancar A, Lindsey-Boltz LA, Gaddameedhi S, Selby CP, Ye R, Chiou YY, Kemp MG, Hu J, Lee JH, Ozturk N (2014): Circadian Clock, Cancer, and Chemotherapy, Biochemistry, (epub ahead of print).
Ye R, Selby CP, Chiou Y, Dagliyan I, Gaddameedhi S, and Sancar A (2014): Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock, Genes & Development, 28:1989-1998.
Kemp MG, Gaddameedhi S, Hu J, Choi JH, and Sancar A (2014): DNA Repair Synthesis and Ligation Affect the Processing of Excised Oligonucleotides Generated by Human Nucleotide Excision Repair, The Journal of Biological Chemistry, (Epub ahead of print).
Choi JH, Gaddameedhi S, Hu J, Kemp MG, and Sancar A (2014): Highly specific and sensitive method for measuring nucleotide excision repair kinetics of UV photoproducts in human cells, Nucleic Acids Research, 42 (4), E29 (1-11).
Hu J, Choi JH, Gaddameedhi S, Kemp MG, Reardon JT, and Sancar A (2013): Nucleotide Excision Repair in Human Cells: Fate of the Excised Oligonucleotide Carrying DNA Damage In Vivo. The Journal of Biological Chemistry, 288: 20918-20926.
Lee JH, Gaddameedhi S, Ozturk N, Ye R and Sancar A (2013): DNA damage-specific control of cell death by cryptochrome in p53 mutant Ras-transformed cells. Cancer Research, 73 (2): 785-791.
Gaddameedhi S, Reardon JT, Ye R, Ozturk N and Sancar A (2012): Effect of circadian clock mutations on DNA damage response in mammalian cells. Cell Cycle, 11(18): 3481-3491. Selected for News & Views by Cell Cycle
Gaddameedhi S, Selby CP, Kaufmann WK, Smart RC, and Sancar A (2011): Control of Skin Cancer by the Circadian Rhythm. Proc Natl Acad Sci USA, 108 (46): 18790-18795.
Selected for commentary and front page highlight by PNAS
Selected by Faculty of 1000 Biology twice by two independent investigators
Gaddameedhi S and Sancar A (2011): Melanoma and DNA Damage from a Distance (Farstander Effect). Pigment Cell & Melanoma Research, 24: 3-4.
Gaddameedhi S, Kemp MG, Reardon JT, Shields J, Smith-Roe SL, Kaufmann WK, and Sancar A (2010): Similar Nucleotide Excision Repair Capacity in Melanocytes and Melanoma Cells. Cancer Research, 70(12):4922-4930.
Ozturk N, Lee JH, Gaddameedhi S and Sancar A (2009): Loss of cryptochrome reduces cancer risk in p53 mutant mice. Proc Natl Acad Sci USA, 106 (8): 2841-2846. Selected by Faculty of 1000 Biology
Gaddameedhi S and Chatterjee S (2009): Association between Unfolded Protein Response, induced by 2-deoxyglucose, and hypersensitivity to cisplatin: A mechanistic study employing molecular genomics. Journal of Cancer Research and Therapeutics, 5(9): 61-66.
Ana D. Simonovic, Gaddameedhi S and Marc D. Anderson (2004): In-gel precipitation of enzymatically released phosphate. Analytical Biochemistry, 334: 312-317.