Shobhan Gaddameedhi, Ph.D.

Education
Ph.D. in pharmaceutical sciences, North Dakota State University, Fargo, N.D.

Master of Science in plant sciences, University of Hyderabad, Hyderabad, India

Bachelor of Science in biology and chemistry, Osmania University, Hyderabad, India

Additional Training & Fellowship
Postdoctoral fellow, Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, N.C. Mentor: Professor Aziz Sancar, MD, Ph.D.

Graduate summer intern, Division of Hematology/Oncology, Amgen, Thousand Oaks, Calif.

Research assistant, Department of Microbiology & Cell Biology, Indian Institute of Science (IISc), Bangalore, India

Research intern, International Crops Research Institute for Semi-Arid Tropics (ICRISAT), Hyderabad, India

Teaching
Dr. Shobhan Gaddameedhi has a mentoring certificate award and a teaching certificate from the UNC Chapel Hill. His teaching focuses on pharmacodynamics and applied therapeutics.

Research
"The circadian clock is the molecular time-keeping system that maintains daily rhythms in physiological and biochemical processes of an organism. Expression of as many as 10% of mammalian genes are regulated by the circadian clock. While the role of the circadian clock in regulation of diurnal changes of physiology in metabolically active organs, such as the liver, fat and muscle, is well known, less is known for skin, which primarily performs protective functions against harmful environmental factors such as ultraviolet radiation (UVR) from sunlight.

Recently, we found that the capacity for nucleotide excision repair (NER) of UV- and other DNA damage in mouse skin oscillates with a circadian rhythm. In addition to NER oscillation, we have shown that DNA replication is circadian in nature in proliferating tissues such as the skin and intestine. This circadian rhythm of NER is anti-phase to that of DNA replication. Both NER and replication are critical for maintenance of genomic stability, and presumably also for melanoma and non-melanoma skin cancer prevention.

The malignant transformation of melanocytes, which comprise a small fraction of total skin cells, leads to the development of melanoma, the deadliest form of skin cancer, and its incidence is increasing dramatically in the United States. Exposure to solar UVR is a major risk factor for melanoma development. UVR acts as an initiator, causing mutations in important melanoma oncogenes/tumor-suppressors, and as a promoter, through immune system modulation such as sunburn-mediated inflammation and immunosuppression.

One of the major goals of my laboratory is to understand the role of the biological clock in melanocyte biology and sunburn inflammatory response, and understand control mechanisms for susceptibility to environmental melanoma. These studies establish a rationale for chrono-photobiological response and suggest that timing or modulating the circadian clock mechanism may reduce the risk of exposure to sunlight and other sources of radiation.

Another long term goal of my research is to investigate the therapeutic potential of chronotherapy against cancer (chrono chemotherapy). Growing evidence suggest a possible benefit of chronotherapy in advanced stages of various types of cancer. However, due to the lack of knowledge of the molecular mechanisms behind these experimental observations has limited the standardization of chrono chemotherapy in to clinical practice.

Using chronopharmacological strategies in circadian clock disrupted genetic mouse models, my studies aim to identify candidate genes or pathways and to define the functional status of circadian clock proteins both in normal tissues and in tumors that determine the timing of cellular sensitivity to radiation treatment and anti-cancer therapeutic drugs. The information generated by these studies may be used to develop drugs and optimal treatment regimens against cancer or to be used in combination with existing therapeutic strategies to improve the therapeutic index of a given therapeutic treatment through the intrinsic circadian clock mechanism."

-Dr. Gaddameedhi

Research Funding Support
K99/R00 NIH Pathway Independent Award: September 2013- August 2018, total amount: $899,078, Role: Principal Investigator

Pilot Project Grant Award (NIH-398 format) from the Center for Environmental Health and Susceptibility (CEHS) at UNC Chapel Hill: April 2013- March 2014, Amount: $25,000, Role: Principal Investigator

NC TraCS $2K Grant Award from the North Carolina Translational and Clinical Sciences (NC TraCS) Institute, 2012, Total Amount: $2,000, Role: Principal Investigator

Pilot Project Grant Award (NIH-398 format) from the Center for Environmental Health and Susceptibility (CEHS) at UNC Chapel Hill: April 2011- March 2012, Amount: $25,000, Role: Principal Investigator

Additional Information

Service
Serving as a reviewer for the following journals: Archives of Toxicology, Biochemistry, Cancer Research, Chemical Research in Toxicology, Chronobiology International, Journal of Bioequivalence & Bioavailability, Pharmaceutical Biology, Photochemistry and Photobiology, Pigment Cell & Melanoma Research, and Plos ONE.

Serving as an editorial board member for International Journal of Cancer Studies & Research (IJCR).

Participated in “Cutaneous Oncology and the Road to Personalized Care at UNC” organized by UNC Lineberger Cancer Center on February 29th, 2012 to synthesize research ideas to develop future research platform in the field of oncology.

Participated in UNC summer undergraduate student research program (delivered research presentation, conducted journal club meeting, and served as a judge in their poster presentation) at UNC Chapel Hill in summer 2011.

Honors & Awards
2013 | Postdoctoral Award for Research Excellence from UNC Chapel Hill

2013 | Travel Award to attend Young Investigator Meeting in India

2012 | Best Poster Award (3rd place) from the Postdoctoral Research Poster Forum of the 2nd annual Oliver Smithies Nobel Symposium at UNC Chapel Hill

2011 | Environmental Mutagen Society (EMS) New Investigator Travel Award

2006 | PRACS Institute Graduate Student Research Award in recognition of research interests, academic excellence and professional leadership at NDSU

1999 | Merit Scholarship Award for being ranked number 1 (All India Rank 1) on the “entrance examination” at the University of Hyderabad

Selected Publications
Choi JH, Gaddameedhi S, Hu J, Kemp MG, 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, 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, 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, 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, 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, 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, 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, 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, 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.

Simonovic AD, Gaddameedhi S, Anderson MD.(2004): In-gel precipitation of enzymatically released phosphate. Analytical Biochemistry, 334: 312-317.

Book Chapter
Chatterjee S, Gaddameedhi S. (2011): In-Depth Look: anti-TNF-α Therapies, Pages 1045-1092. (Title of the Book: Development of Therapeutic Agents Handbook, Edited by Gad Shayne Cox, ISBN-13: 978-0-471-21385-7 - John Wiley & Sons)

updated 04/15/2014     Back to top
Dr. Shobhan Gaddameedhi

Assistant Professor
Experimental and Systems Pharmacology

shobhan.gaddameedhi@wsu.edu

Office: PBS 317
P.O. Box 1495
Washington State University
Spokane, WA 99210-1495