Daniel Matson

EDUCATION

MD – University of Virginia
PhD – University of Virginia

RESEARCH SUMMARY

Disorders of the blood and bone marrow are of great public health significance. During development and in the adult bone marrow, a relatively small number of critical transcription factors promote complex and diverse cellular processes to bring about faithful and timely hematopoiesis. The mechanisms by which these factors interface with chromatin to modulate gene expression, and the partner factors that are critical for this function, are the primary research focus of the Matson Laboratory. In addition, we are increasingly interested in the role played by hematopoietic transcription factors in cancers of the gynecologic tract, especially uterine serous carcinoma.

RESEARCH DETAIL

GATA2 Interactors as Critical Regulators of Hematopoiesis

GATA2 binds at GATA nucleotide sequences throughout the genome to orchestrate complex genetic programs. However, it does not act alone, and other critical transcription factors such as RUNX1, SCL/TAL1, PU.1, and ERG have been demonstrated to co-localize with GATA2 on chromatin in various contexts. Identifying additional factors that interact or co-localize with GATA2 on chromatin is likely to elucidate novel mechanisms via which hematopoietic cells regulate processes such as self-renewal, proliferation, and differentiation. We are using unbiased proteomic-based approaches to identify such proteins and characterize their functions in benign and malignant hematopoiesis, with the goal of discovering novel biology in the area of hematopoiesis.

Uterine Serous Carcinoma

Uterine serous carcinoma (USC) is an aggressive epithelial malignancy that occurs in older women and has a 5 year survival rate as low as 50%. Approximately half of these patients will present with advanced disease at diagnosis, and even a subset of those patients with apparently localized (surgically resectable) disease will ultimately show disease progression. Unfortunately, at the moment there are very few prognostic markers in USC to guide the clinical care of USC patients. In part for this reason, virtually all USC patients will be recommended to receive cytoreductive chemotherapy if they can tolerate it. We have found that GATA2 is unexpectedly expressed in a subset of endometrial serous carcinomas where it portends an excellent prognosis. Our laboratory is currently elucidating the mechanism(s) by which GATA2 acts in USCs to bring about this effect, and are evaluating whether GATA2 may serve as a clinically actionable prognostic marker.

Myelodysplastic Syndrome and Acute Myeloid Leukemia

Germline mutations in GATA2 lead to the GATA2 Deficiency Syndrome, which predisposes to bone marrow failure and acute myeloid leukemia via unknown mechanisms. Sporadic GATA2 mutations can also be found in cases of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) where their significance is unknown. GATA2 RNA transcripts are elevated in MDS and AML and GATA2 is hypothesized to form a positive feedback loop with p38 in AML cells which promotes AML proliferation. In acute promyelocytic leukemia (a subtype of AML), GATA2 has been proposed to behave as a tumor suppressor by suppressing PML-RARA-driven cell growth. GATA2 is also a critical regulator of benign hematopoietic stem cells and it is believed to maintain this function in leukemic stem cells. GATA2 RNA transcripts may also be elevated in a subset of pediatric B-acute lymphoblastic leukemias where the significance of this finding is unclear. Finally, GATA2 is predicted to be specific for the myeloid lineage by RNA expression studies. Critically, GATA2 protein levels have never been measured in MDS or acute leukemia. In collaboration with Dr. Emery Bresnick’s laboratory, we are utilizing unique anti-GATA2 antibodies to evaluate GATA2 levels in human bone marrow biopsies from patients with MDS and AML in order to further elucidate the role for this critical factor in these disease processes.

Translational Biology

A core purpose of my laboratory also includes working to translate laboratory findings into the clinic, and as a practicing hematopathologist I maintain a strong connection to both benign and malignant patient tissue repositories. Our overarching goal is to discover new biology that improves our understanding of hematopoiesis and informs the development of future clinical diagnostics and patient therapies.

SELECTED PUBLICATIONS

https://www.ncbi.nlm.nih.gov/myncbi/daniel.matson.1/bibliography/public/

Robbins DJ, Pavletich TS, Patil AT, Pahopos D, Lasarev M, Polaki US, Gahvari ZJ, Bresnick EH, Matson DR. Linking GATA2 to myeloid dysplasia and complex cytogenetics in adult myelodysplastic neoplasm and acute myeloid leukemia. Blood Adv. 2024 Jan 9;8(1):80-92.

Rajagopalan A, Feng Y, Gayatri MB, Ranheim EA, Klungness T, Matson DR, Lee MH, Jung MM, Zhou Y, Gao X, Nadiminti KV, Yang DT, Tran VL, Padron E, Miyamoto S, Bresnick EH, Zhang J. A gain-of-function p53 mutant synergizes with oncogenic NRAS to promote acute myeloid leukemia in mice. J Clin Invest. 2023 Dec 15;133(24):e173116.

Patil AT, Bennett DD, Xu J, Weisman P, Matson DR. Spatial transcriptomics of a giant pilomatricoma. J Cutan Pathol. 2023 Nov;50(11):963-970. doi: 10.1111/cup.14524. Epub 2023 Aug 30.

Mehta C, Fraga de Andrade I, Matson DR, Dewey CN, Bresnick EH. RNA-regulatory exosome complex confers cellular survival to promote erythropoiesis. Nucleic Acids Res. 2021 Jun 1.

Reinig EF, Rubinstein JD, Patil AT, Schussman AL, Horner VL, Kanagal-Shamanna R, Churpek JE, Matson DR. Needle in a haystack or elephant in the room? Identifying germline predisposition syndromes in the setting of a new myeloid malignancy diagnosis. Leukemia. 2023 Aug;37(8):1589-1599.

Smeenk L, Ottema S, Mulet-Lazaro R, Ebert A, Havermans M, Arricibita Varea A, Fellner M, Pastoors D, van Herk S, Erpelinck-Verschueren C, Grob T, Hoogenboezem RM, Kavelaars FG, Matson DR, Bresnick EH, Bindels EM, Kentsis A, Zuber J, Delwel R. Selective requirement of MYB for oncogenic hyperactivation of a translocated enhancer in leukemia. Cancer Discov. 2021 May 12.

Matson DR, Denu RA, Zasadil LM, Burkard ME, Weaver BA, Flynn C, Stukenberg PT. High nuclear TPX2 expression correlates with TP53 mutation and poor clinical behavior in a large breast cancer cohort, but is not an independent predictor of chromosomal instability. BMC Cancer. 2021 Feb 23;21(1):186.

Ray S, Chee L, Matson DR, Palermo NY, Bresnick EH, Hewitt KJ. Sterile α-motif domain requirement for cellular signaling and survival. J Biol Chem. 2020 May 15;295(20):7113-7125.

Castaño J, Aranda S, Bueno C, Calero-Nieto FJ, Mejia-Ramirez E, Mosquera JL, Blanco E, Wang X, Prieto C, Zabaleta L, Mereu E, Rovira M, Jiménez-Delgado S, Matson DR, Heyn H, Bresnick EH, Göttgens B, Di Croce L, Menendez P, Raya A, Giorgetti A. GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm. Stem Cell Reports. 2019 Sep 10;13(3):515-529.

Matson DR, Yang DT. Autoimmune Lymphoproliferative Syndrome: An Overview. Arch Pathol Lab Med. 2020 Feb;144(2):245-251.

Matson DR, Hardin H, Buehler D, Lloyd RV. AKT activity is elevated in aggressive thyroid neoplasms where it promotes proliferation and invasion. Exp Mol Pathol. 2017 Dec;103(3):288-293.

Hewitt KJ, Katsumura KR, Matson DR, Devadas P, Tanimura N, Hebert AS, Coon JJ, Kim JS, Dewey CN, Keles S, Hao S, Paulson RF, Bresnick EH. GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia. Dev Cell. 2017 Aug 7;42(3):213-225.

Matson DR, Stukenberg PT. CENP-I and Aurora B act as a molecular switch that ties RZZ/Mad1 recruitment to kinetochore attachment status. J Cell Biol. 2014 May 26;205(4):541-54.

Matson DR, Demirel PB, Stukenberg PT, Burke DJ. A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint. Genes Dev. 2012 Mar 15;26(6):542-7.