Michael Kelley
Professor of Medicine
Overview
1. A major theme throughout my career has been the biology of and improving outcomes for patients with lung cancer. Early publications examined the relationship between specific genetic alterations in lung cancer and clinically relevant applications including differential drug sensitivity, differentiation of metastases from second primary cancers, and application of patient-specific mutations as epitopes for immunotherapy. Correlation of alteration of p16 with drug sensitivity led to identification of a class of CDK4 inhibitor. I served as the primary investigator or co-investigator in all of these studies. I led a study that demonstrated that tubulin mutations are uncommon in lung cancer and described the artifactual detection of pseudogenes as the origin of a prior report claiming association of tubulin mutation with taxane sensitivity, thus correcting the scientific record.
2. A second area of continuing interest in lung cancer is the conduct of therapeutic and prevention clinical trials. These trials have primarily been translation of hypotheses derived primarily from laboratory-based biological observations including the GRP autocrine growth factor in small cell lung cancer, a phase I study of a pulmonary toxin in non-small cell lung cancer, mutation-specific immunotherapy, and a putative chemopreventive agent for smokers. More recently, I have been an active member of the Respiratory Committee of CALGB/Alliance including serving as principal investigator on a trial testing the addition of irinotecan to treatment of patients with small cell lung cancer.
3. Through my clinical practice, I identified a large family with the May-Hegglin anomaly, an autosomal dominant platelet condition characterized as thrombocytopenia, leukocyte inclusions, and giant platelets. While the condition had been described in the early 1900s, the genetic basis was unknown. I conceptualized and led a project to identify the underlying molecular basis of this frequently misdiagnosed disorder through classical genetics. I then extended that observation to related genetic conditions (now known as MYH9-assocaited disorders) characterized by varying degrees of hematological abnormalities, hearing loss and renal disease. Analysis of the spectrum of observed mutations and phenotypes resulted in identification of a genotype-phenotype association for the most medically significant aspects of the disorders. Working with Dan Kiehart’s lab, we described the effect of commonly observed mutations of MYH9 on assembly of non-muscle myosin. An animal model of the most common MYH9 mutation was created in my lab and demonstrated hematological abnormalities similar to those found in humans.
4. I described genetic linkage for a rare familial cancer syndrome characterized by very high penetrance of chordoma. Subsequent linkage analysis resolved a phenotype mis-assignment and resulted in identification of germline gene duplication of the T-box gene, Brachyury in about half of affected families. I then confirmed another groups report that a common coding region SNP of the Brachyury gene as well as additional genetic variants are associated with an increased risk for development of chordoma independent of amplification of the Brachyury gen. To study the biology of chordoma, I established the origin of existing putative chordoma cell lines and working criteria for identification of possible new chordoma cell lines. Using two confirmed chordoma cell lines, I screened all regulatory-approved drugs for anti-growth activity to determine whether any could be repurposed for clinical use in patients.
5. Beginning in 2007, I began to transition my career to a leadership position within the Department of Veterans Affairs as the National Program Director for Oncology. This led to opportunities to utilize the vast and detailed clinical data sets of nearly 1 million patients with cancer to address questions that have been difficult to study either through randomized trials or in less robust datasets. The use of surgery to treat early stage non-small cell lung cancer is a standard treatment for which I observed a racial disparity. The lower rate of use of surgery among African Americans was not explained by association with comorbidity. In another study, I described the rate of use of adjuvant chemotherapy as having increased temporally after publication of randomized trials showing a modest benefit to its use. I showed that initially this chemotherapy was primarily carboplatin-based, despite all positive trials having used cisplatin. Cisplatin use has subsequently increased though there is not a demonstrable improvement is survival associated with its use. I also showed that survival overall, regardless of use of chemotherapy, has improved suggesting that the application of clinical trial data for adjuvant chemotherapy is improving outcome. In a related study, I found that elderly patients benefit as much as younger patients from adjuvant chemotherapy. Patients with stage III non-small cell lung cancer are frequently treated with concurrent chemoradiotherapy, for which there are two commonly used chemotherapy regimens: cisplatin-etoposide and carboplatin-paclitaxel. I examined the outcome and toxicity of patients treated with these two regimens and found that while there was no significant difference in survival, there was more toxicity associated with cisplatin-etoposide. This finding may impact one current clinical guideline recommendation that favors cisplatin-etoposide over carboplatin-paclitaxel. Finally, in stage IV disease, a similar observation was made that cisplatin-based chemotherapy is associated with greater toxicity but not improved survival.
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/michael.kelley.1/bibliography/43511621/public/?sort=date&direction=descending
Positions
Professor of Medicine in the School of Medicine
2014 School of Medicine
Member of the Duke Cancer Institute in the School of Medicine
1998 School of Medicine
Education
M.D. 1985
1985 University of Michigan, Ann Arbor
Medical Resident, Medicine
1988 Duke University
Publications, Grants & Awards
- Grants (25)
- Conference Pages (76)
- Academics Articles (199)
National Institutes of Health
Department of Defense
National Institutes of Health
Department of Defense
National Institutes of Health
AstraZeneca Pharmaceuticals, LP
AstraZeneca Pharmaceuticals, LP
AstraZeneca Pharmaceuticals, LP
Durham Veterans Affairs Medical Center
Chordoma Foundation
Chordoma Foundation
Veterans Administration Medical Center
National Institutes of Health
Veterans Administration Medical Center
Veterans Administration Medical Center
National Institutes of Health
Veterans Administration Medical Center
National Institutes of Health
Veterans Administration Medical Center
Veterans Administration Medical Center
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Thoracic Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Oncology Nursing Forum
Journal of Thoracic Oncology
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal for Immunotherapy of Cancer
The Journal of Molecular Diagnostics
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
International Journal of Radiation Oncology, Biology, Physics
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
International Journal of Radiation Oncology, Biology, Physics
International Journal of Radiation Oncology, Biology, Physics
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
International Journal of Radiation Oncology, Biology, Physics
Value in Health
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Hepatology (Baltimore, Md.)
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Molecular Biology of the Cell
Journal of Thoracic Oncology
International Journal of Radiation Oncology, Biology, Physics
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Process Development Division - Core Programming Topic at the 2011 AIChE Annual Meeting
Molecular Biology of the Cell
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Lung Cancer (Amsterdam, Netherlands)
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
American Journal of Human Genetics
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
American Journal of Human Genetics
Jco Precision Oncology
Jco Oncol Pract
Jco Oncol Pract
Jco Oncol Pract
Jco Precision Oncology
Cancer Medicine
Jco Precision Oncology
J Cancer Res Clin Oncol
European Journal of Cancer
Jco Clinical Cancer Informatics
Jco Oncol Pract
Jco Precision Oncology
Jco Clinical Cancer Informatics
Pharmacogenomics
Bmc Health Services Research
Cancer Treatment and Research Communications
Jco Precision Oncology
Federal Practitioner : for the Health Care Professionals of the Va, Dod, and Phs
Cancer Epidemiol Biomarkers Prev
J Natl Compr Canc Netw
Jco Precision Oncology
Plos One
J Oncol Pract
Int J Radiat Oncol Biol Phys
J Womens Health (Larchmt)
J Natl Compr Canc Netw
Cancer Management and Research
Semin Oncol
Jco Precision Oncology
Journal of Registry Management
Hepatology Communications
Clin Breast Cancer
J Thorac Oncol
Mil Med
Cancer Epidemiol Biomarkers Prev
Bmc Medical Informatics and Decision Making
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Federal Practitioner : for the Health Care Professionals of the Va, Dod, and Phs
Jama Internal Medicine
Cancer Invest
Clinical Colorectal Cancer
Clinical Cancer Research
Int J Radiat Oncol Biol Phys
Int J Radiat Oncol Biol Phys
J Thorac Oncol
Annals of the American Thoracic Society
Cancer Epidemiol Biomarkers Prev
Annals of Translational Medicine
Annals of the American Thoracic Society
Journal of Thoracic Oncology
Journal of Thoracic Oncology
Journal of Thoracic Oncology
Cancer
J Geriatr Oncol
Nicotine Tob Res
Journal of Clinical Oncology
J Neurosurg Spine
Ann Intern Med
Cancer
Journal of Aids & Clinical Research
Bmj Open Respiratory Research
European Journal of Cancer
Journal of Clinical Oncology
Journal of Clinical Oncology
Am J Health Promot
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology
Journal of Clinical Oncology
Journal of Clinical Oncology
Ann Intern Med
Contemp Clin Trials
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology
The New England Journal of Medicine
Biophysical Journal
Oncology (Williston Park, N.Y.)
Oncology (Williston Park, N.Y.)
Journal of Clinical Oncology
Proc Natl Acad Sci U S A
J Thorac Oncol
J Gen Intern Med
Journal of Thoracic Oncology
Journal of Clinical Oncology
J Pain
Laboratory Investigation
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
The Journal of Clinical Investigation
Nature Medicine
Journal of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Nature Medicine
Journal of Clinical Oncology
Lung Cancer (Amsterdam, Netherlands)
Nature Medicine
Journal of Thoracic Oncology
The New England Journal of Medicine
Journal of Clinical Oncology
Journal of Clinical Oncology
International Journal of Cancer
Lung Cancer (Amsterdam, Netherlands)
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
British Journal of Haematology
American Journal of Medical Genetics. Part A
Journal of Clinical Oncology
American Journal of Medical Genetics. Part A
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Journal of Clinical Oncology
Haematologica
Seminars in Oncology
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Cancer Chemotherapy and Pharmacology
Proceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics
Journal of the National Cancer Institute
Journal of the National Cancer Institute
Journal of the National Cancer Institute
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
American Journal of Human Genetics
American Journal of Human Genetics
American Journal of Human Genetics
American Journal of Human Genetics
Human Genetics
Human Genetics
Genes, Chromosomes & Cancer
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
American Journal of Human Genetics
Molecular and Cellular Probes
Oncology (Williston Park, N.Y.)
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Lung Cancer (Amsterdam, Netherlands)
Oncology (Williston Park, N.Y.)
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Proceedings of the National Academy of Sciences of the United States of America
International Immunology
Proceedings of the National Academy of Sciences of the United States of America
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
International Journal of Cancer
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Seminars in Respiratory and Critical Care Medicine
Journal of Investigative Medicine
International Journal of Cancer
International Journal of Cancer
Lung Cancer (Amsterdam, Netherlands)
Journal of the National Cancer Institute
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Cancer Letters
American Journal of Respiratory and Critical Care Medicine
Advances in Internal Medicine
Proceedings of the National Academy of Sciences of the United States of America
Offices & Contact
Durham, NC
27705 Duke Box 3396
Durham, NC
27710