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Dr. Paul T. Henderson

Paul Henderson, Ph.D.Dr. Paul T. Henderson is an Assistant Adjunct Professor in the Department of Internal Medicine / Hematology & Oncology Division at the University of California, Davis Medical Center in Sacramento, CA and a CBST Member.  His research interestfocuses on the use of accelerator mass spectrometry to measure small amounts of drugs bound to DNA (DNA adducts), which provides a measure of the cells' propensity to take up the drug, form, and repair DNA damage.  These characteristics vary greatly in tumor cells, and Dr. Henderson's laboratory is interested in compiling such information as a means to predict which cancer patients respond to chemotherapy.  Research in the Henderson laboratory also focuses on utilization of cell-free protein expression to make nanolipoprotein particles (NLPs), which can be "coexpressed" with membrane proteins such as GPCRs and ERRB2 (HER2).


Dr. Henderson received his B.S. in Chemistry at the University of Florida where he studied photoinduced electron transfer chemistry (artificial photosynthesis) as an undergraduate researcher. He earned his PhD in Organic Chemistry from the Georgia Institute of Technology.    At Georgia Tech he researched the use of DNA as a molecular wire and found, along with others, that DNA is a semiconductor that can potentially be used in molecular electronics.  One of the limitations of using DNA as a wire is that currently passing through the strand causes damage to the nucleotides in the DNA.  This damage is identical to that caused in cellular DNA by oxidative stress, which led to a NIH Postdoctoral Fellowship at MIT, where Dr. Henderson studied DNA damage and repair in the Division of Biological Engineering.  Following his Fellowship, he started as an independent scientist at Lawrence Livermore National Laboratory in 2002, where he used their advanced mass spectrometry technology to study DNA damage and repair caused by oxidative stress and by chemotherapy drugs that target tumor DNA.


Research interests and projects in Dr. Henderson's lab include:

-  Studying how drugs bind to DNA in cells, with the goal of using that information to predict which patients will respond to chemotherapy.

 
- Dog and human clinical studies are in progress to evaluate carboplatin-DNA damage as a biomarker of response to therapy for lung and bladder cancer. 


- Use of nanoparticles to express functional receptors that are important for understanding breast cancer, such as ERBB2 (HER2), which is the target of the successful anticancer drug Herceptin (Trastuzumab).  Recently, Dr. Henderson's laboratory has synthesized this receptor outside of the cell, which may allow previously unattainable structural and biochemical studies.

Members of the Henderson Laboratory (co-managed with Dr. Chong-Xian Pan, MD, PhD from UCD):

Dr. Henderson contributes expertise in DNA damage and repair.  Dr. Pan provides clinical and research expertise.  The Henderson/Pan group has Sisi Wang as a graduate student, Cindy Lin, DVM, PhD as a Postdoctoral Fellow, Hongyong Zhang DVM, PhD as a Research Associate, Yanchun Wang, MD, PhD, a visiting professor from Ji Lin Medical College, and several student volunteers, including Candice Gellner.


Selected List of Publications (selected from 27 peer reviewed publications and 3 patents):
1. Li, Y.; Shawgo, R.S.; Tyler, B.; Henderson, P.T.; Vogel, J.S.; Rosenburg, A.; Langer, R.; Brem, H.; Cima, M.J. In vivo Release From a Drug Delivery MEMS Device Journal of Controlled Drug Release, 2004,100, 211-219.

2. Hah, S.S.; Stivers, K.M.; de Vere White, R.; Henderson, P.T. Kinetics of Carboplatin-DNA Binding in Genomic DNA and Bladder Cancer Cells As Determined by Accelerator Mass Spectrometry, Chemical Research in Toxicology, 2006, 19, 622-626.

3. Hah, S.S.; Mundt, J.M.; Kim, H.M.; Sumbad, R.A.; Turteltaub, K.W.; Henderson, P.T.Measurement of 7,8-dihydro-8-oxo-2'-deoxyguanosine metabolism in MCF-7 cells at low concentrations using accelerator mass spectrometry, Proceedings of the National Academy of Sciences,USA, 2007, 104, 27, 11203-11208 (cover article).

4. Hah, S.S.; Sumbad, R.A.; de Vere White, R.; Turteltaub, K.W.; Henderson, P.T.Characterization of Oxaliplatin-DNA Adduct Formation in DNA and Differentiation of Cancer Cell Drug Sensitivity at Microdose Concentrations, Chemical Research in Toxicology 2007, 20(12), 1745-1751.

5. Coldwell, K.; Cutts, S.; Henderson, P.T.; Ognibene, T.; Phillips, D. Detection of Adriamycin-DNA adducts by Accelerator Mass Spectroscopy at clinically relevant Adriamycin concentrations Nucleic Acids Research, 2008, 36, 16, e100.

6. Cooke M.S.; Henderson, P.T.; Evans, M.D. Source and significance of extracellular, oxidatively-modified DNA lesions, Journal of Clinical Biochemistry and Nutrition, 2009, 45(3), 255-70.

7. Hah SS, Henderson PT, Turteltaub, KW Recent advances in biomedical applications of accelerator mass spectrometry, Journal of Biomedical Science, 2009, 16, 111.

8. Coldwell K, Cutts SM, Ognibene TJ, Henderson PT, Phillips, DR. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry.  Methods Mol. Biol. 2010, 613, 103-18.

9. Microdosing for prediction of patient response. Henderson PT, Pan C-X, Bioanalysis, 2010,In press.


Outside interests:

Include skiing, hockey and bicycling.


Contact:
Paul T. Henderson, PhD

Assistant Professor

Division of Hematology and Oncology

Department of Internal Medicine

UC Davis Medical Center, Sacramento, CA 95817

Phone: (925)570-1615 (cell)

e-mail: paul.henderson@ucdmc.ucdavis.edu


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