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.

Kristen Jacobsen

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

Undergraduate:

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. 

Email: dawnbarnes@emory.edu


Deb DeRyckere, PhD

Undergraduate:

Graduate Studies: 

Post-doctoral:

Fun Fact:

Email: deborah.deryckere@emory.edu


Douglas K. Graham, MD PhD


Justus Huelse, MS

Undergraduate: University of Konstanz, Germany

Graduate Studies: University of Copenhagen, Denmark

Current Project: 

Fun Fact: I like to make my own cheeses.

Email: justus.hulse@emory.edu


  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!

                                                   Email: kristen.jacobsen@emory.edu 


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

Fun Fact:

Email: katherine.minson@emory.edu


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.

Pubmed

Email: Ryanjsumme@emory.edu


Dan Yan, MD PhD

Graduate: Tongji Medical School, China

Pubmed

Fun Fact: Shopping, cooking, planting and traveling with my family to places that I've never been are things I enjoy.

Email: danyan2@emory.edu


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.

Email: rebecca.elizabeth.parker@emory.edu 

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.

PubMed

2017 Journal Title First Author Journal
1/4/17 Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies Mihalis S. Kariolis The Journal of Clinical Investigation
1/11/17 Freezing effects on the acute myeloid leukemia cell proteome and phosphoproteome revealed using optimal quantitative workflows Elise Aasebo Journal of Proteomics
1/18/17 The receptor tyrosine kinase AXL mediates nuclear translocation of the epidermal growth factor receptor Toni Brand Science Signaling
2/1/17 Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer Louise Carter Nature Medicine
2/8/17 EGFR inhibitors exacerbate differentiation and cell cycle arrest induced by retinoic acid and vitamin D3 in acute myeloid leukemia cells Elodie Lainey Cell Cycle
3/8/17 Phosphatidlyserine sensing by TAM receptors regulates AKT-dependent chemoresistance and PD-L1 expression Canan Kasikara Molecular Cancer Research
3/15/17 Autocrine and paracrine interactions between multiple myeloma cells and bone marrow stromal cells by growth arrest-specific gene 6 crosstalk with interleukin 6 Miki Furukawa JBC Papers
3/29/17 FGF2 from marrow microenvironment promotes resistance to FLT3 inhibitors in acute myeloid leukemia Elie Traer Cancer Research
4/5/17 Biobanking of patient and patient-derived xenograft ovarian tumor tissue: efficient preservation with low and high fetal calf serum based methods

Nicolette G. Alkema

Scientific Reports
4/26/17 Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity Stanley G. Kimani

Scientific Reports

...

 

   
8/2/17

Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

R. Mallone Clinical and Experimental Immunology 

 

 

 Madeline Huey, BA

 Undergraduate: University of Colorado, Boulder CO

 Last  Project: Understand mechanisms of bone marrow resistance to MERTK inhibition.

 Fun Fact: I love to cook and try new recipes!