The receptor tyrosine kinase MERTK was first discovered by Dr. Graham and subsequent work in the Graham lab demonstrated oncogenic roles for MERTK in a variety of solid tumor and hematologic malignancies. Current projects focused on acute leukemia, non-small cell lung cancer, glioblastoma, and melanoma are aimed at better understanding the biology of MERTK and related receptors in tumor cells and their roles in the human immune system. In addition, in collaboration with scientists at the University of North Carolina, the Graham lab developed and characterized a series of novel small molecules that selectively and potently inhibit MERTK with the goal of targeting MERTK to treat patients with cancer, including MRX-2843, a first-in-class MERTK/FLT3-selective small molecule inhibitor that will advance to phase I clinical trials in 2018. Studies to determine the optimal application of MERTK inhibitors in combination with other agents to maximize therapeutic effects are ongoing.
Determine mechanisms of resistance to targeted MERTK inhibition.
Identify roles and effects of MERTK inhibition in early thymic precursor acute lymphoblastic leukemia.
Elucidate molecular pathways that can be targeted in combination with MERTK inhibition in acute myeloid leukemia.
Determine roles for TYRO-3, a protein related to MERTK, in acute myeloid leukemia.
Develop biomarkers of MERTK inhibition and therapeutic response in acute leukemia cells.
Identify tyrosine kinase inhibitors that synergize with MERTK inhibition to suppress tumor growth.
Determine roles for MERTK in resistance to third-generation EGFR tyrosine kinase inhibitors in non-small cell lung cancers with activating EGFR mutations.
Determine immunomodulatory roles for MERTK in the tumor microenvironment using syngenic mouse models of leukemia and breast cancer.
Identification of immune biomarkers of MERTK inhibition and therapeutic effects.
Dawn Barnes, PhD
Graduate Studies: Emory University, 2016
Current Project: Elucidating the molecular pathways that synergize with MERTK inhibition in acute myeloid leukemia.
Fun Fact: I enjoy pyrography because it allows me to customize gifts for friends and family.
Deb DeRyckere, PhD
Undergraduate: University of Michigan
Graduate Studies: University of California- Berkeley
Post-doctoral: University of Colorado School of Medicine
Fun Fact: I once spent 3 weeks in the arctic communing with polar bears!
Douglas K. Graham, MD, PhD
Undergraduate: Wake Forest University
Graduate Studies: University of North Carolina (MD, PhD)
Post-doctoral: University of Colorado/Children's Hospital Colorado
Fun Fact: I once rappelled down the tallest building in Denver to raise money for cancer research.
Justus Huelse, MS
Undergraduate: University of Konstanz, Germany
Graduate Studies: University of Copenhagen, Denmark
Fun Fact: I like to make my own cheeses.
Katherine Minson, MD
Undergraduate: University of Pennsylvania
Graduate Studies: Medical University of South Carolina
Residency: Vanderbilt University, Nashville TN
Fellowship: University of Colorado at Denver and Emory University
Current Project: Understand mechanisms of bone marrow resistance to MERTK inhibition and nuclear MERTK.
Rebecca Parker, BS
Undergraduate: Tulane University, New Orleans, LA
Current Project: Mouse colony management and MERTK inhibition in NSCLC.
Fun Fact: I commute every day on my glitter-purple bike.
Sherri Smart, MD, PhD
Ryan Summers, MD
Undergraduate: University of Georgia, Athens GA
Graduate Studies: Emory University School of Medicine, Atlanta GA
Residency: Emory University
Fellowship: Emory University
Fun Fact: I played quarterback for a team that won the high school football state championship in Texas.
Eleana Vasileiadi, MD
Dan Yan, MD PhD
Graduate: Tongji Medical School, China
Fun Fact: Shopping, cooking, planting and traveling with my family to places that I've never been are things I enjoy.
Branchford BR, Stalker TJ, Law L, Acevedo G, Sather S, Brzezinski C, Wilson, KM, Minson K, Lee-Sherick AB, Davizon-Castillo P, Ng C, Zhang W, Neeves KB, Lentz SR, Wang X, Frye SV, Earp HS, DeRyckere D, Brass LF, Graham DK*, and JA Di Paola*. The small molecule MERTK inhibitor UNC2025 decreases platelet activation and prevents thrombosis. J Thromb Haemost. 2018;16(2):352-363. PMID: 29045015
Minson KA, DeRyckere D, and DK Graham. The current state of FLT3 inhibition in acute myeloid leukemia: pitfalls and promises. J Cell Signaling. 2017 2:4. PMID: in process
McIver AL, Zhang W, Liu Q, Jiang X, Stashko MA, Miley MJ, Norris-Drouin J, Machius M, DeRyckere D, Wood E, Graham DK, Earp HS, Kireev D, Frye SV and X Wang. Discovery of Macrocyclic Pyrimidines as Mer-specific Tyrosine Kinase Inhibitors. Chem Med Chem 2017 3;12:207-213. PMID 28032464.
Wang X, Liu J, Zhang W, Stashko MA, Nichols J, Miley MJ, Norris-Drouin J, Chen Z, Machius M, DeRyckere D, Wood E, Graham DK, Earp HS, Kireev D and SV Frye. Design and Synthesis of Novel Macrocyclic Mer Tyrosine Kinase Inhibitors. ACS Med Chem Lett. 2016;7:1044-49. PMID: 27994735
Huey MG, Minson KA, Earp HS, DeRyckere D, and DK Graham. Targeting the TAM Receptors in Leukemia. Cancers (Basel).2016 8;8(11). PMID: 27834816
Sufit A, Lee-Sherick L, DeRyckere D, Rupji M, Dwivedi B, Varella-Garcia M, Pierce AM, Kowalski J, Wang X, Frye SV, Earp S, Keating AK, and DK Graham. MERTK inhibition induces polyploidy leading to cell death and cellular senescence in glioblastoma multiforme. PloS One, 2016;11:e0165107. PMID: 27783662
DeRyckere D, Lee-Sherick AB, Huey M, Hill AA, Tyner JW, Jacobsen KM, Page LS, Kirkpatrick GG, Eryildiz F, Montgomery SA, Zhang W, Wang X, Frye SV, Earp HS and DK Graham. UNC2025, a MerTK small molecule inhibitor, is therapeutically effective alone and in combination with methotrexate in leukemia models. Clin Cancer Res, 2017;23:1481-1492. PMID: 27649555
Minson K, Smith C, DeRyckere D, Libbrecht C, Lee-Sherick A, Huey M, Lasater E, Kirkpatrick G, Stashko M, Zhang W, Jordan CT, Kireev D, Wang X, Frye S, Earp S, Shah N and DK Graham. A novel MERTK/FLT3 inhibitor, MRX-2843, overcomes resistance-conferring FLT3-ITD mutations in AML. J Clin Invest Insight, 2016;1:e85630. PMID: 27158668.
Cummings CT, Zhang W, Davies KD, Kirkpatrick GD, Zhang D, DeRyckere D, Wang X, Frye SV, Earp HS, and DK Graham. Small molecule inhibition of MERTK is efficacious in non-small cell lung cancer models independent of driver oncogene status. Mol Cancer Ther 2015;14:2014-22. PMID: 26162689.
Lee Sherick A, Zhang W, Menachof K, Hill A, Rinella S, Stashko M, Jordan C, Wei Q, Liu J, Zhang D, DeRyckere D, Wang X, Frye S, Earp HS, and DK Graham. Efficacy of a dual Mer and Flt3 tyrosine kinase small molecule inhibitor, UNC1666, in acute myeloid leukemia. Oncotarget, 2015;6:6722-6736. PMID: 25762638.
Graham DK, DeRyckere D, Davies KD, and Earp HS. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 2014;14:769-85.
Alvarez-Caldero F, Gregory MA, Pham-Danis C, DeRyckere D, Stevens B, Zaberezhnyy V, Hill A, Gemta L, Kumar A, Kumar V, Wempe W, Pollyea DA, Jordan CT, Serkova N, Graham DK, and J DeGregori. Tyrosine kinase inhibition results in mitochondrial metabolic addictions in leukemia. Clin Cancer Res, 2015;21:1360-72. PMID: 25547679
Cummings CT, Linger RM, Cohen RA, Sather S, Kirkpatrick GD, Davies KD, DeRyckere D, Earp HS and DK Graham. Mer590, a novel monoclonal antibody targeting MER receptor tyrosine kinase, decreases colony formation and increases chemosensitivity in non-small cell lung cancer. Oncotarget, 2014;5:10434-45. PMID: 25372020.
Zhang W, DeRyckere D, Hunter D, Liu J, Stashko M, Minson KA, Cummings CC, Lee M, Glaros TG, Newton DL, Sather S, Zhang D, Kireev DB, Janzen WP, Earp HS, Graham DK, Frye SV, and X Wang. UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor. J Med Chem. 2014;57:7031-7041. PMID: 25068800.
Kristen Jacobsen (2009-2017), graduate student, Integrated Department of Immunology
Christopher Cummings (2011-2015), graduate student, Medical Scientist Training Program (MSTP)
Alisa Lee Sherick, MD (2010-2015), pediatric hematology/oncology fellow
Alexandra Sufit (2014-2015), graduate student, Cancer Biology
Lenka Teodorovic, PhD (2013-2015) postdoctoral fellow
Sandra Christoph, MD, PhD (2011-2013), postdoctoral fellow
Amy Keating, MD (2003-2013), pediatric hematology/oncology fellow
Rachel Linger, PhD (2007-2012), postdoctoral fellow
Justine Migdall, (2009-2012), graduate student, Medical Scientist Training Program (MSTP)
Luis Pessoa-Brandao, PhD, (2007-2012), postdoctoral fellow
Jennifer Schlegel (2010-2012), graduate student, Program in Molecular Biology
Kristen Eisenman, MD (2008 - 2011), pediatric hematology/oncology fellow
Kelly Sawczyn, MD (2004-2007), pediatric hematology/oncology fellow
Dana Salzberg, MD (2002-2006), pediatric hematology/oncology fellow
Leukemia and Lymphoma Society - Development of a novel FLT3 tyrosine kinase inhibitor with activity against D835Y and F691L mutant proteins
Swim Across America Research Grant - Development of a Novel Therapy Targeting MERTK and STAT5 in AML Stem Cells
CURE Childhood Cancer - MERTK Inhibitor Combination Therapy for Treatment of AML
American Cancer Society - Development of biomarkers of sensitivity to MRX2843, a dual MERTK and FLT3 inhibitor for treatment of acute myeloid leukemia in children
Precious Jules Foundation – Therapeutic targeting of MERTK and BCL-2 in Early T-Precursor acute lymphoblastic leukemia
Development of small molecule MERTK inhibitors for treatment of cancer
Stephen V. Frye, H. Shelton Earp III, Xiaodong Wang, Dmitri Kireev, University of North Carolina
Mediators of resistance to MERTK inhibition in acute myeloid leukemia
Jeff Tyner, Oregon Health Sciences University
Targeting MERTK for anti-thrombotic applications
Jorge DiPaola, Brian Branchford, University of Colorado
MERTK as a mediator of resistance to AXL-targeted therapies
Deric Wheeler, University of Wisconsin
Interactions between MERTK and STAT5 in leukemia stem cells
Kevin Bunting, Zhengqi Wang, Emory University
Roles for MERTK in glioblastoma
Dolores Hambardzumyan, Emory University
Nanoscale combination therapies for treatment of acute lymphoblastic leukemia
Erik Dreaden, Emory University
TAM kinases as mechanisms of resistance to chemotherapy in acute myeloid leukemia
Andy Kolb, Erin Crowgey, Nemours Hospital for Children & University of Delaware