Michael John Kelley, MD

Professor of Medicine
Member of the Duke Cancer Institute
Campus mail 508 Fulton St; Hem-onc 111G, Durham, NC 27705
Phone (919) 286-0411
Email address michael.kelley@duke.edu

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

Education and Training

  • Medical Resident, Medicine, Duke University, 1985 - 1988
  • M.D., University of Michigan at Ann Arbor, 1985

Publications

Boyer, MJ, Williams, CD, Harpole, DH, Onaitis, MW, Kelley, MJ, and Salama, JK. "Improved Survival of Stage I Non-Small Cell Lung Cancer: A VA Central Cancer Registry Analysis." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 12, no. 12 (December 2017): 1814-1823.

PMID
28951090
Full Text

Cechova, S, Dong, F, Chan, F, Kelley, MJ, Ruiz, P, and Le, TH. "MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and Migration." Journal of the American Society of Nephrology : JASN (October 9, 2017).

PMID
28993503
Full Text

Lynch, JA, Berse, B, Chun, D, Rivera, D, Filipski, KK, Kulich, S, Viernes, B, DuVall, SL, and Kelley, MJ. "Epidermal Growth Factor Receptor Mutational Testing and Erlotinib Treatment Among Veterans Diagnosed With Lung Cancer in the United States Department of Veterans Affairs." Clinical lung cancer 18, no. 4 (July 2017): 401-409.

PMID
28038980
Full Text

Zullig, LL, Sims, KJ, McNeil, R, Williams, CD, Jackson, GL, Provenzale, D, and Kelley, MJ. "Cancer Incidence Among Patients of the U.S. Veterans Affairs Health Care System: 2010 Update." Military medicine 182, no. 7 (July 2017): e1883-e1891.

PMID
28810986
Full Text

Paulus, JK, Williams, CD, Cossor, FI, Kelley, MJ, and Martell, RE. "Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer-Response." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 26, no. 6 (June 2017): 977-. (Letter)

PMID
28506970
Full Text

Efimova, O, Berse, B, Denhalter, DW, DuVall, SL, Filipski, KK, Icardi, M, Kelley, MJ, and Lynch, JA. "Clinical decisions surrounding genomic and proteomic testing among United States veterans treated for lung cancer within the Veterans Health Administration." BMC medical informatics and decision making 17, no. 1 (May 30, 2017): 71-.

PMID
28558785
Full Text

Kinsinger, LS, Anderson, C, Kim, J, Larson, M, Chan, SH, King, HA, Rice, KL, Slatore, CG, Tanner, NT, Pittman, K, Monte, RJ, McNeil, RB, Grubber, JM, Kelley, MJ, Provenzale, D, Datta, SK, Sperber, NS, Barnes, LK, Abbott, DH, Sims, KJ, Whitley, RL, Wu, RR, and Jackson, GL. "Implementation of Lung Cancer Screening in the Veterans Health Administration." JAMA internal medicine 177, no. 3 (March 2017): 399-406.

PMID
28135352
Full Text

Chun, DS, Berse, B, Venne, VL, DuVall, SL, Filipski, KK, Kelley, MJ, Meyer, LJ, Icardi, MS, and Lynch, JA. "BRCA testing within the Department of Veterans Affairs: concordance with clinical practice guidelines." Familial cancer 16, no. 1 (January 2017): 41-49.

PMID
27589855
Full Text

Kelley, MJ, Jha, G, Shoemaker, D, Herndon, JE, Gu, L, Barry, WT, Crawford, J, and Ready, N. "Phase II Study of Dasatinib in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer." Cancer investigation 35, no. 1 (January 2017): 32-35.

PMID
27911119
Full Text

Zullig, LL, Smith, VA, Jackson, GL, Danus, S, Schnell, M, Lindquist, J, Provenzale, D, Weinberger, M, Kelley, MJ, and Bosworth, HB. "Colorectal Cancer Statistics From the Veterans Affairs Central Cancer Registry." Clinical colorectal cancer 15, no. 4 (December 2016): e199-e204.

PMID
27301717
Full Text

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