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. 

Email: dawnbarnes@emory.edu


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!

Email: deborah.deryckere@emory.edu


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.

Email: justus.hulse@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.

Email: katherine.minson@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 


Sherri Smart, MD, PhD

Undergraduate:

Graduate:

Current Project:

Fun Fact:

Email:


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.

Email: Ryanjsumme@emory.edu


Eleana Vasileiadi, MD

Undergraduate:

Graduate:

Current Project:

Fun Fact:

Email:


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.

Email: danyan2@emory.edu

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.

 

2018 Journal Title First Author Journal
1/10/18

A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer.

Frederick H. Wilson Cancer Cell
1/17/18

JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias.

C. Delgado-Martin Leukemia
1/31/18

A genomic screen identifies TYRO3 as a MITF regulator in melanoma.

Shoutian Zhu PNAS
2/7/18

FLT3-driven redox-modulation of Ezrin regulates leukaemic cell migration.

Aoife Corcoran Free Radical Research
2/21/18

Combination of galectin inhibitor GCS-100 and BH3 mimetics eliminates both p53 wild type and p53 null AML cells.

Peter P. Ruvolo

Biochimica et Biophysica Acta

3/7/18

UNC569-induced Morphological Changes in Pigment Epithelia and Photoreceptor Cells in the Retina through MerTK Inhibition in Mice.

Ayako Sayama Toxicologic Pathology
3/14/18

Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease.

Miles A. Miller Chemical Communications
3/21/18

Concurrent alterations in EGFR-mutant lung cancers associated with resistance to EGFR kinase inhibitors and characterization of MTOR as a mediator of resistance.

Helena A. Yu Clinical Cancer Research

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

...

 

   
7/12/17

Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin-3, and Mer Tyrosine Kinase.

K. Normura The Journal of Immunology
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 

8/16/17

Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer.

 

Ken Uchibori Nature Communications
9/20/17

mTORC1/autophagy-regulated MerTK in mutant BRAFV600 melanoma with acquired resistance to BRAF inhibition.

Gongda Xue Oncotarget
10/4/17

JAK1/2 and BCL2 inhibitors synergize to counteract bone marrow stromal cell-induced protection of AML.

R. Karjalainen Blood
10/11/17

Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.

Yong Tang PLOS One
11/1/17

Expression and role of TYRO3 and AXL as potential therapeutical targets in leiomyosarcoma.

Carmela Dantas-Barbosa

British Journal of Cancer
11/8/17

Bone marrow stroma-mediated resistance to FLT3 inhibitors in FLT3-ITD AML is mediated by persistent activation of extracellular regulated kinase.

Xiaochuan Yang Bristish Journal of Haematology
11/29/17

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers.

Collin M. Blakely Nature Genetics
12/6/17

A permanent window for the murine lung enables high-resolution imaging of cancer metastasis.

David Entenberg Nature Methods
12/13/17

Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6.

Ke Geng Frontiers in Immunology

 

 

 

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