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Sleep and Performance Research Center

Environmental Carcinogenesis and Circadian Rhythm

Shobhan Gaddameedhi, M.Sc., Ph.D.

Areas of Interest

Circadian Clock, Shift work, Genotoxic Stress, Cancer, DNA Repair, Chronotherapy.

Research Scope

Every cell in the body has a circadian clock that regulates biochemical and cellular processes such as sleep, body temperature, metabolism, hormone levels and physiology. Human and mouse models suggest that approximately 50% of protein coding genes display circadian rhythmicity at the transcriptional level. There are more than 170 drug targets among these clock-controlled genes, some of which are acted on by 56 of the top 100 best-selling drugs in the US. There is a high correlation between advent of circadian disruption through shift work and development of several cancer types as per the data accumulated from animal experimental studies and human epidemiological studies. There is no concrete evidence reported, however, at the cellular and molecular levels for humans. In this regard the Gaddameedhi lab currently pursuing the following projects:

Research Focus

  • Identify the cellular and molecular mechanisms regulating genomic instability and carcinogenesis via circadian disruption by shift work.
  • Understand the effect of circadian clock on skin biology via environmental stresses associated with dermatological perturbations including skin cancer.
  • Unravel the molecular basis for chronopharmacology role in improved efficacy of genotoxic stress mediated cancer therapeutics.

The long-term goal is to translate the general principles of circadian clock that govern environmental carcinogenesis and to improved therapeutic efficacies of current anti-cancer modalities

Students and Staff

  • Kenneth Porter, M.S. (Laboratory manager/Research Intern)
  • Bala SC Koritala, Ph.D. (Postdoctoral Fellow)
  • Panshak P. Dakup, B.S. (PhD Candidate, Pharmaceutical Sciences)
  • Sam Sarkar, M.S. (Ph.D. Candidate, Pharmaceutical Sciences)
  • Jinita Modasia, B. Pharm. (Ph.D. Candidate, Pharmaceutical Sciences)

Techniques

  • Real-time cell culture and small animal bioluminescence imaging for circadian phase analysis and tumorigenesis
  • Gene expression analysis (multiplex, qRT-PCR, RNAseq.)
  • Chromatin immunoprecipitation
  • Quantitative immuno-slot blot and western blot analysis
  • Immunohistochemistry and confocal imaging

Resources

  • Ultraviolet radiation (UV-A/B/C), Ionizing radiation (X-RAD 320 model) and Cisplatin treatments, Shift work simulation and Luminometer for circadian biology studies
  • Mammalian cell lines (normal and tumor cells)
  • Genetically engineered mouse models (GEMMs)
  • Circadian synchronized human tissue biopsies

Grant Support

  • National Institutes of Health

Publications

http://www.ncbi.nlm.nih.gov/pubmed/?term=gaddameedhi+s