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Dario Marchetti, PhD

Professor of Biomarkers Research, Institute for Academic Medicine
Full Member, Research Institute
Director, Biomarker Research Program
Houston Methodist


Marchetti Lab


dmarchetti@houstonmethodist.org
Biography

Dario Marchetti, Ph.D., tumor and molecular biologist, is the Director of the Biomarker Research Program at Houston Methodist Research Institute and Professor of Biomarkers Research at Houston Methodist.  Dr. Marchetti formerly served as the “Jack L. Titus” endowed Professor at Baylor College of Medicine, and currently holds a visiting Professor appointment in the Department of Molecular & Cellular Biology at Baylor College of Medicine.

Dr. Marchetti is an internationally recognized authority in the field of circulating tumor cells (CTCs). CTCs and CTC-based biomarker signatures can be clinically useful tools for monitoring cancer progression in the patient in "real-time;" and for combating cancer metastasis for improved patient outcome as prime examples of precision medicine. With keen insights into the biology of brain metastasis, Dr. Marchetti pioneered models by discovering molecular determinants underlying brain metastasis and biomarker properties of brain metastasis-associated and brain-colonizing CTCs. As a consummate scientist, Dr. Marchetti’s bibliography include 180 publications of which 80 are in peer-reviewed journals in the fields of neuroscience and oncology. He has received numerous awards and secured uninterrupted funding since 1990 by receiving grants from federal, state, institutional and private agencies. He is a reviewer for the most prominent journals in cancer research and sits on editorial boards of “Cancer Microenvironment, “Vascular Cell”, "Clinical & Experimental Pathology", "International Journal of Oncology", “Cancer Letters”, “Journal of Cellular Biochemistry”, “Discovery/Discovery Reports” (a journal from Harvard Medical School) and "Cancer Metastasis Reviews" among others. Dr. Marchetti also acts as Guest Editor on a special tome on brain metastasis by the International Journal of Molecular Sciences (Basel, Switzerland) and an invited Editor on a special volum on CTCs by Frontiers Research Topic Oncology (Lausanne Switzerland). Further, he serves as standing member on grant reviewing panels of the National Institutes of Health of USA and Italy, the Department of Defense of the US, and is frequently invited as grant reviewer and consultant for multiple national and international agencies and pharma companies devoted to oncology research.

Dr. Marchetti graduated from the University of Pavia, Italy in 1979. He worked as postdoctoral fellow at the University of Illinois, Chicago (1980-1982) and the University of Texas Medical Branch – Galveston (Texas) (1984-1986). He then became a research scientist at the University of Texas Health Science Center-Houston (1986-1991), Research Associate and later Instructor at MD Anderson Cancer Center (1992-1999), Assistant Professor at UT-Houston (1999-2001), Associate Professor and later Professor (with tenure) at LSU-Baton Rouge, Louisiana (2002-2007), Professor with tenure at Baylor College of Medicine (2008-2015) prior to joining the Faculty of Houston Methodist Hospital (September 2015).

Description of Research

Scientific focus of Dr. Marchetti’s laboratory is to investigate the biology, properties and clinical utilities of Circulating Tumor Cells (CTCs) directly isolated from cancer patients and “seeds” of fatal metastatic disease. Metastasis, the major cause of cancer patients’ mortality (>90% of cancer deaths). CTCs are proving to be potent prognostic and diagnostic tools for noninvasive "real-time" assessment of cancer progression (the concept of "liquid biopsy”).  Evaluation of CTCs and CTC biomarkers can enable a more sensitive monitoring of treatment efficacy, thus guiding drug selection in adjuvant settings where no such tools exist today.  However, current technologies prevent researchers from identifying the majority of the CTCs from cancer patients that metastasize within the body, e.g., to brain.  Brain metastasis represents an urgent clinical problem which is increasing in frequency with dismal patient survival rates.  Brain metastasis are estimated to become the No. 1 cancer killer and the number of patient cases with brain metastasis already outnumber breast cancer cases in the U.S. alone.

Dr. Marchetti and team are working to develop a vigorous biomarker research program with Houston Methodist Hospital faculty across numerous disciplines with a primary focus on breast cancer brain metastasis. One of his key priorities is to better understand why breast cancer reoccurs and how to decipher the molecular heterogeneity of CTC phenotypes which are responsible for seeding/reseeding metastasis leading to patients’ death.

Areas Of Expertise

Circulating tumor cells CTC subsets profiling Brain metastasis Breast cancer Melanoma Heparanase Tumor microenvironment Cancer stem cells Diagnostic biomarkers
Publications

Molecular characterization of breast cancer CTCs associated with brain metastasis
Boral, D, Vishnoi, M, Liu, HN, Yin, W, Sprouse, ML, Scamardo, A, Hong, DS, Tan, TZ, Thiery, JP, Chang, JC & Marchetti, D 2017, Nature Communications, vol 8, no. 1, 196. DOI:

Molecular characterization of breast cancer CTCs associated with brain metastasis
Boral, D, Vishnoi, M, Liu, HN, Yin, W, Sprouse, ML, Scamardo, A, Hong, DS, Tan, TZ, Thiery, JP, Chang, JC & Marchetti, D 2017, Nature Communications, vol 8, no. 1, 196. DOI:

The isolation and characterization of CTC subsets related to breast cancer dormancy
Vishnoi, M, Peddibhotla, S, Yin, W, Scamardo, AT, George, GC, Hong, DS & Marchetti, D 2015, Scientific reports, vol 5, 17533. DOI:

Oncogenic role of Merlin/NF2 in glioblastoma
Guerrero, PA, Yin, W, Camacho, L & Marchetti, D 2015, Oncogene, vol 34, no. 20, pp. 2621-30. DOI:

Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes
Caruana, I, Savoldo, B, Hoyos, V, Weber, G, Liu, H, Kim, ES, Ittmann, MM, Marchetti, D & Dotti, G 2015, Nature Medicine, vol 21, no. 5, pp. 524-529. DOI:

Heparanase mediates a novel mechanism in lapatinib-resistant brain metastatic breast cancer
Zhang, L, Ngo, JA, Wetzel, MD & Marchetti, D 2015, Neoplasia (United States), vol 17, no. 1, pp. 101-113. DOI:

MicroRNA and Protein Profiling of Brain Metastasis Competent Cell-Derived Exosomes
Camacho, L, Guerrero, P & Marchetti, D 2013, PLoS ONE, vol 8, no. 9, e73790. DOI:

The identification and characterization of breast cancer CTCs competent for brain metastasis
Zhang, L, Ridgway, LD, Wetzel, MD, Ngo, J, Yin, W, Kumar, D, Goodman, JC, Groves, MD & Marchetti, D 2013, Science Translational Medicine, vol 5, no. 180, 180ra48. DOI:

Heparanase-induced GEF-H1 signaling regulates the cytoskeletal dynamics of brain metastatic breast cancer cells
Ridgway, LD, Wetzel, MD, Ngo, JA, Erdreich-Epstein, A & Marchetti, D 2012, Molecular Cancer Research, vol 10, no. 6, pp. 689-702. DOI:

Selection of brain metastasis-initiating breast cancer cells determined by growth on hard agar
Guo, L, Fan, D, Zhang, F, Price, JE, Lee, JS, Marchetti, D, Fidler, IJ & Langley, RR 2011, American Journal of Pathology, vol 178, no. 5, pp. 2357-2366. DOI:

Heparanase modulates Shh and Wnt3a signaling in human medulloblastoma cells
Ridgway, LD, Wetzel, MD & Marchetti, D 2011, Experimental and Therapeutic Medicine, vol 2, no. 2, pp. 229-237. DOI:

MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase
Zhang, L, Sullivan, PS, Goodman, JC, Gunaratne, PH & Marchetti, D 2011, Cancer Research, vol 71, no. 3, pp. 645-654. DOI:

Modulation of GEF-H1 induced signaling by heparanase in brain metastatic melanoma cells
Ridgway, LD, Wetzel, MD & Marchetti, D 2010, Journal of Cellular Biochemistry, vol 111, no. 5, pp. 1299-1309. DOI:

Epidermal growth factor-induced heparanase nucleolar localization augments DNA topoisomerase I activity in brain metastatic breast cancer
Zhang, L, Sullivan, P, Suyama, J & Marchetti, D 2010, Molecular Cancer Research, vol 8, no. 2, pp. 278-290. DOI:

Cell surface heparan sulfate released by Heparanase promotes melanoma cell migration and angiogenesis
Roy, M & Marchetti, D 2009, Journal of Cellular Biochemistry, vol 106, no. 2, pp. 200-209. DOI:

HIP/RPL29 antagonizes VEGF and FGF2 stimulated angiogenesis by interfering with HS-dependent responses
DSouza, S, Yang, W, Marchetti, D, Muir, C, Farach-Carson, MC & Carson, DD 2008, Journal of Cellular Biochemistry, vol 105, no. 5, pp. 1183-1193. DOI:

Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation
Brown, AJ, Alicknavitch, M, DSouza, SS, Daikoku, T, Kirn-Safran, CB, Marchetti, D, Carson, DD & Farach-Carson, MC 2008, Bone, vol 43, no. 4, pp. 689-699. DOI:

Neurotrophin receptors and heparanase: A functional axis in human medulloblastoma invasion
Marchetti, D, Mrak, RE, Paulsen, DD & Sinnappah-Kang, ND 2007, Journal of Experimental and Clinical Cancer Research, vol 26, no. 1, pp. 5-23.

Biocatalytic and antimetastatic studies of the marine cembranoids sarcophine and 2-epi-16-deoxysarcophine
Sawant, SS, Youssef, DTA, Reiland, J, Ferniz, M, Marchetti, D & El Sayed, KA 2006, Journal of Natural Products, vol 69, no. 7, pp. 1010-1013. DOI:

Heparanase expression and TrkC/p75NTR ratios in human medulloblastoma
Sinnappah-Kang, ND, Mrak, RE, Paulsen, DB & Marchetti, D 2006, Clinical and Experimental Metastasis, vol 23, no. 1, pp. 55-63. DOI: