From left to right:
D. DeRyckere, M. Huey, K. Jacobsen, K. Minson, D. Yan, J. Huelse, S. Zheng, D. Graham
The receptor tyrosine kinase, MERTK, was first discovered by Dr. Graham in 1995 and has since been implicated in a variety of solid tumor and hematologic malignancies. In collaboration with the University of North Carolina we have developed and characterized a series of novel small molecules that selectively and potently inhibit the TAM receptors. Our lab has ongoing projects in the areas of Non-Small Cell Lung cancer, Glioblastoma, Acute Leukemias and Melanoma aimed at better understanding the biology of the TAM family of receptor tyrosine kinases, their role in the human immune system and the effects of their inhibition on tumor cell survival and immunomodulation. With our collaborators, we have developed a series of novel, MERTK inhibitors with potent selectivity compared to other RTK's. Indeed, MRX-2843 is a first-in class, MERTK/FLT3 selective small molecule inhibitor that has been approved by the FDA for use in a phase I clinical trial.
- Investigate mechanisms of bone marrow resistance to targeted MERTK inhibition.
- Identify roles and effects of MERTK inhbition in ETP T-ALL.
- Elucidate the molecular pathways that synergize with MERTK to inhibit acute myeloid leukemia cellular proliferation.
Katherine Minson, Madeline Huey, Ryan Summers, Dawn Barnes
- Identify tyrosine kinase inhibitors that act synergistically with MERTK inhibition to suppress NSCLC cell line expansion and xenograft tumor growth.
- Understand resistance mechanisms to EGFR tyrosine kinase inhibitors for NSCLC with activating EGFR mutations.
Dan Yan, Justus Huelse
- Investigate mechanisms of immunomodulation of MERTK in syngenic mouse models of leukemia and breast cancer by MERTK inhibition.
MERTK and glioblastoma - Dolores Hambardzumyan, Emory University
Small molecule inhibitor and patient sample screens - Jeff Tyner, Oregon University of Health and Science
Small molecule inhibitor development and characterization - Xiaodong Wang, Stephen V. Frye, Shelton H. Earp, University of North Carolina
Dawn Barnes, PhD
Graduate Studies: Emory University, 2016
Current Project: Elucidating the molecular pathways that synergize with MERTK inhibition in acute myeloid leukemia.
Deb DeRyckere, PhD
Douglas K. Graham, MD PhD
Madeline Huey, BA
Undergraduate: University of Colorado, Boulder CO
Current Project: Understand mechanisms of bone marrow resistance to MERTK inhibition.
Fun Fact: I love to cook and try new recipes!
Justus Huelse, MS
Undergraduate: University of Konstanz, Germany
Graduate Studies: University of Copenhagen, Denmark
Fun Fact: I like to make my own cheeses.
Kristen Jacobsen, PhD
Undergraduate: Suny Geneseo, Geneseo NY
Graduate Studies: University of Colorado, Denver CO
Current Project: Immunomodulation of MERTK in PyMT and Acute Myeloid Leukemia syngeneic mouse models
Fun Fact: I have rocked more than 15 different hair colors!
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
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.
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.
Huey MG, Minson KA, Earp HS, DeRyckere D, Graham DK. Targeting the TAM Receptors in Leukemia. Cancers (Basel). 2016 Nov 8;8(11). Review.
Sufit A, Lee-Sherick AB, DeRyckere D, Rupji M, Dwivedi B, Varella-Garcia M, Pierce AM, Kowalski J, Wang X, Frye SV, Earp HS, Keating AK, Graham DK. MERTK Inhibition Induces Polyploidy and Promotes Cell Death and Cellular Senescence in Glioblastoma Multiforme. PLoS One. 2016 Oct 26;11(10). Article.
DeRyckere D, Lee-Sherick AB, Huey MG, Hill AA, Tyner JW, Jacobsen KM, Page LS, Kirkpatrick GG, Eryildiz F, Montgomery SA, Zhang W, Wang X, Frye SV, Earp HS, Graham DK. UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and In Combination with Methotrexate in Leukemia Models. Clin Cancer Research. 2016 Sep 20. Article.
Lee-Sherick AB, Eisenman KM, Sather S, McGranahan A, Armistead PM, McGary CS, Hunsucker SA, Schlegel J, Martinson H, Cannon C, Keating AK, Earp HS, Liang X, DeRyckere D, Graham DK. Aberrant Mer Recepter Tyrosine Kinase Expression Contributes to Leukemogenesis in Acute Myeloid Leukemia. Oncogene. 2016 Dec 1;35(48):6270. Article.
Minson KA, Smith CC, DeRyckere D, Libbrecht C, Lee-Sherick AB, Huey MG, Lasater EA, Kirkpatrick GD, Stashko MA, Zhang W, Jordan CT, Kireev D, Wang X, Frye SV, Earp HS, Shah NP, Graham DK. The MERTK/FLT3 Inhibitor MRX-2843 Overcomes Resistance-Conferring FLT3 Mutations in Acute Myeloid Leukemia. JCI Insight. 2016 Mar;1(3). Article.
Cummings CT, Zhang W, Davies KD, Kirkpatrick GD, Zhang D, DeRyckere D, Wang X, Frye SV, Earp HS, Graham DK. Small Molecule Inhibition of MERTK is Efficacious in Non-Small Cell Lung Cancer Models Independent of Driver Oncogene Status. Mol Cancer Ther. 2015 Sep;14(9):2014-22. Article.
Lee-Sherick AB, Zhang W, Menachof KK, Hill AA, Rinella S, Kirkpatrick G, Page LS, Stashko MA, Jordan CT, Wei Q, Liu J, Zhang D, DeRyckere D, Wang X, Frye S, Earp HS, Graham DK. Efficacy of a Mer and Flt3 Tyrosine Kinase Small Molecule Inhibitor, UNC1666, in Acute Myeloid Leukemia. Oncotarget. 2015 Mar 30;6(9):6722-36. Article.
Graham DK, DeRyckere D, Davies KD, Earp HS. The TAM Family: Phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 2014 Dec;14(12):769-85. Review.
Cummings CT, Linger RM, Cohen RA, Sather S, Kirkpatrick GD, Davies KD, DeRyckere D, Earp HS, Graham DK. Mer590, A Novel Monoclonal Antibody Targeting MER Receptor Tyrosine Kinase, Decreases Colony Formation and Increases Chemosensitivity in Non-Small Cell Lung Cancer. Oncotarget. 2014 Nov 15;5(21)10434-45.