Photo of Matthew R. Ramsey,  PhD

Matthew R. Ramsey, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-5775

Matthew R. Ramsey, PhD

Brigham And Women's Hospital


  • Assistant Professor, Dermatology, Harvard Medical School
  • Research Associate, Dermatology, Brigham And Women's Hospital


Research Abstract

Maintaining proper tissue homeostasis involves careful regulation of cellular proliferation and survival in stem and transient amplifying cells. This is particularly true of the epidermis, which undergoes a constant process of proliferation, stratification, and differentiation. The epidermis is particularly susceptible to environmental damage, and unchecked proliferation of damaged cells can lead to cancer. Tumor suppressors such as p16INK4a and p53 serve the important function of causing growth arrest or apoptosis of damaged cells, but this has the unfortunate consequence of reducing normal tissue regenerative potential. In addition, there are many positive regulators of proliferation and stem cell function that when inappropriately activated can promote tumorigenesis. Thus, the combination of aberrant activation of normal growth regulators combined with the loss of tumor suppressors in epithelial tissues can lead to tumor development.

Squamous Cell Carcinoma (SCC) is a common cancer that develops in stratified epithelial tissues such as the epidermis, the oral cavity, and the lungs. While cutaneous SCC can usually be managed surgically, unresectable SCC has few effective treatments, resulting in more than 7,000 deaths every year. SCC tumors found in the head & neck region (HNSCC) and the lungs (Squamous NSCLC) have much poorer prognosis, as surgical options are often limited. Despite intense study, the current lack understanding of the molecular genetics of SCC has resulted in little progress in improving overall survival of overall survival of patients with HNSCC, squamous NSCLC, and aggressive cutaneous SCC. Therefore, it is essential to gain a better molecular understanding of the genetic events driving SCC in order to find new targets for treatment.

The Ramsey laboratory is focused on exploring the mechanisms that drive SCC, in order to develop more targeted and effective therapies. We use tissue-specific activation of driving oncogenes combined with inactivation of tumor suppressors to develop pre-clinical SCC models which contain genetic alterations seen in human SCC which can be used to test novel therapeutics and elucidate how specific combinations of lesions cause the development of SCC tumors. To complement this work, we have also developed a variety of biochemical systems to investigate the role of transcription factors and associated co-factors in driving SCC-specific transcription. These tools can be applied to study the large variety of transcription factors that contribute to the pathogenesis of SCC. Understanding the differences in transcriptional networks between normal and cancerous tissues will offer insight into the vulnerabilities of SCC tumors that can be therapeutically targeted to improve the survival and quality of life of patients.

Publications from Harvard Catalyst Profiles

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  • Schatton T, Itoh Y, Martins C, Rasbach E, Singh P, Silva M, Mucciarone KN, Heppt MV, Geddes-Sweeney J, Stewart K, Brandenburg A, Liang J, Dimitroff CJ, Mihm MC, Landsberg J, Schlapbach C, Lian CG, Murphy GF, Kupper TS, Ramsey MR, Barthel SR. Inhibition of melanoma cell-intrinsic Tim-3 stimulates MAPK-dependent tumorigenesis. Cancer Res 2022. PubMed
  • Boudra R, Woappi Y, Wang D, Xu S, Wells M, Schmults CD, Lian CG, Ramsey MR. Regulation of 5-hydroxymethylcytosine by TET2 contributes to Squamous Cell Carcinoma tumorigenesis. J Invest Dermatol 2021. PubMed
  • Sato K, Parag-Sharma K, Terajima M, Musicant AM, Murphy RM, Ramsey MR, Hibi H, Yamauchi M, Amelio AL. Lysyl hydroxylase 2-induced collagen cross-link switching promotes metastasis in head and neck squamous cell carcinomas. Neoplasia 2021; 23:594-606. PubMed
  • Cuevas-Nunez MC, Gomes CBF, Woo SB, Ramsey MR, Chen XL, Xu S, Xu T, Zhan Q, Murphy GF, Lian CG. Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2017. PubMed
  • Best SA, Nwaobasi AN, Schmults CD, Ramsey MR. CCAR2 Is Required for Proliferation and Tumor Maintenance in Human Squamous Cell Carcinoma. J Invest Dermatol 2017; 137:506-512. PubMed
  • Ramsey MR, Wilson C, Ory B, Rothenberg SM, Faquin W, Mills AA, Ellisen LW. FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma. J Clin Invest 2013; 123:3525-38. PubMed
  • Gallant-Behm CL, Ramsey MR, Bensard CL, Nojek I, Tran J, Liu M, Ellisen LW, Espinosa JM. ΔNp63α represses anti-proliferative genes via H2A.Z deposition. Genes Dev 2012; 26:2325-36. PubMed
  • Ramsey MR, He L, Forster N, Ory B, Ellisen LW. Physical association of HDAC1 and HDAC2 with p63 mediates transcriptional repression and tumor maintenance in squamous cell carcinoma. Cancer Res 2011; 71:4373-9. PubMed
  • Ory B, Ramsey MR, Wilson C, Vadysirisack DD, Forster N, Rocco JW, Rothenberg SM, Ellisen LW. A microRNA-dependent program controls p53-independent survival and chemosensitivity in human and murine squamous cell carcinoma. J Clin Invest 2011; 121:809-20. PubMed
  • Johnson SM, Torrice CD, Bell JF, Monahan KB, Jiang Q, Wang Y, Ramsey MR, Jin J, Wong KK, Su L, Zhou D, Sharpless NE. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J Clin Invest 2010; 120:2528-36. PubMed
  • Harvey KF, Mattila J, Sofer A, Bennett FC, Ramsey MR, Ellisen LW, Puig O, Hariharan IK. FOXO-regulated transcription restricts overgrowth of Tsc mutant organs. J Cell Biol 2008; 180:691-6. PubMed
  • Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Janne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK. LKB1 modulates lung cancer differentiation and metastasis. Nature 2007; 448:807-10. PubMed
  • Ramsey MR, Krishnamurthy J, Pei XH, Torrice C, Lin W, Carrasco DR, Ligon KL, Xiong Y, Sharpless NE. Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues. Cancer Res 2007; 67:4732-41. PubMed
  • Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 2006; 443:453-7. PubMed
  • Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE. Ink4a/Arf expression is a biomarker of aging. J Clin Invest 2004; 114:1299-307. PubMed
  • Sharpless NE, Ramsey MR, Balasubramanian P, Castrillon DH, DePinho RA. The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and tumorigenesis. Oncogene 2004; 23:379-85. PubMed
  • Rheinwald JG, Hahn WC, Ramsey MR, Wu JY, Guo Z, Tsao H, De Luca M, Catricalà C, O'Toole KM. A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol Cell Biol 2002; 22:5157-72. PubMed