Sean Christensen, MD, PhD
Research & Publications
Sean Christensen, MD, PhD, is an Assistant Professor of Dermatology whose research is focused on the elucidation of cellular and molecular mechanisms of skin cancer development and the application of this knowledge to clinical patient care. It is well established that ultraviolet radiation is the primary driver of skin cancer pathogenesis, but the cellular and genetic events that drive the expansion and progression of malignant precursors in the skin remain poorly understood. An unexplored aspect of gene expression in the epidermis is post-transcriptional regulation by RNA binding proteins. By reducing mRNA stability and translation efficiency, RNA-binding proteins, such as Pumilio 1 and 2, can coordinately regulate the expression of large sets of functionally related genes and maintain genomic stability in response to DNA injury. In collaboration with Dr. Haifan Lin, who originally defined the role of Pumilio proteins in stem cell function, Dr. Christensen has identified a role for Pumilio proteins in regulating the response of epidermal keratinocytes to ultraviolet radiation. Two major goals of Dr. Christensen’s laboratory research are to define the mechanism by which Pumilio proteins promote genomic stability and to define the consequences of impaired Pumilio function on ultraviolet-induced mutation, clonal expansion and cancer development.
Dr. Christensen also leads clinical and translational research projects focused on skin cancer prevention and treatment. Working with the Genomics and Bioinformatics Core at the Yale Stem Cell Center, Dr. Christensen has developed a method to identify rare somatic mutations in human skin adjacent to surgically excised skin cancers. Using next generation sequencing technology, this method will investigate the relationship between these ultraviolet-induced somatic mutations and skin cancer risk. In addition to identifying critical mutations for skin cancer pathogenesis, this research could more precisely identify patients for targeted interventions to prevent skin cancer development. Dr. Christensen is also conducting clinical research on surgical and non-surgical treatment of skin cancer, cancer prevention strategies for patients with multiple skin cancers, and management of high risk squamous cell carcinoma and other rare skin cancers, and he serves as principal investigator in a phase III clinical trial of a novel topical treatment for basal cell carcinoma.
Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Skin Neoplasms; Ultraviolet Rays; Keratosis, Actinic
- Predicting outcomes following second intent healing of periocular surgical defectsKibbi N, Khan Y, Leffell DJ, Christensen SR, Suozzi KC. Predicting outcomes following second intent healing of periocular surgical defects Archives Of Dermatological Research 2020, 313: 483-489. PMID: 32833078, DOI: 10.1007/s00403-020-02122-w.
- Photodynamic therapy for cutaneous squamous cell carcinoma in situ: Impact of anatomic location, tumor diameter, and incubation time on effectivenessKibbi N, Zhang Y, Leffell DJ, Christensen SR. Photodynamic therapy for cutaneous squamous cell carcinoma in situ: Impact of anatomic location, tumor diameter, and incubation time on effectiveness Journal Of The American Academy Of Dermatology 2019, 82: 1124-1130. PMID: 31712171, DOI: 10.1016/j.jaad.2019.10.079.
- Comparison of Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive MelanomaCheraghlou S, Christensen SR, Agogo GO, Girardi M. Comparison of Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma JAMA Dermatology 2019, 155: 1252-1259. PMID: 31553403, PMCID: PMC6764120, DOI: 10.1001/jamadermatol.2019.2890.
- Repairs of the EarChristensen S, Stamey C. Repairs of the Ear 2019, 499-521. DOI: 10.1007/978-3-030-02023-1_31.
- Recent advances in field cancerization and management of multiple cutaneous squamous cell carcinomasChristensen SR. Recent advances in field cancerization and management of multiple cutaneous squamous cell carcinomas F1000Research 2018, 7: f1000 faculty rev-690. PMID: 29904586, PMCID: PMC5989149, DOI: 10.12688/f1000research.12837.1.
- Sirolimus-Associated Rapid Progression of Leg Ulcers in a Renal Transplant RecipientTotonchy MB, Colegio OR, Christensen SR. Sirolimus-Associated Rapid Progression of Leg Ulcers in a Renal Transplant Recipient JAMA Dermatology 2017, 153: 105-106. PMID: 27806175, DOI: 10.1001/jamadermatol.2016.3546.
- Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approachChristensen SR, McNiff JM, Cool AJ, Aasi SZ, Hanlon AM, Leffell DJ. Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach Journal Of The American Academy Of Dermatology 2015, 74: 356-362. PMID: 26670714, DOI: 10.1016/j.jaad.2015.09.060.
- Cancer of the SkinChristensen, S.R., and Leffell, D.J. in Cancer: Principles and Practice of Oncology, 10th Edition, Lippincott Williams &Wilkins.
- TLR9 Promotes Tolerance by Restricting Survival of Anergic Anti-DNA B Cells, Yet Is Also Required for Their ActivationNickerson KM, Christensen SR, Cullen JL, Meng W, Prak E, Shlomchik MJ. TLR9 Promotes Tolerance by Restricting Survival of Anergic Anti-DNA B Cells, Yet Is Also Required for Their Activation The Journal Of Immunology 2013, 190: 1447-1456. PMID: 23296704, PMCID: PMC3563726, DOI: 10.4049/jimmunol.1202115.
- Preoperative EvaluationChristensen S, Aasi S. Preoperative Evaluation 2011, 13-33. DOI: 10.1007/978-1-4471-2152-7_3.
- RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexesAvalos AM, Kiefer K, Tian J, Christensen S, Shlomchik M, Coyle AJ, Marshak-Rothstein A. RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes Autoimmunity 2009, 43: 103-110. PMID: 20014975, PMCID: PMC2929824, DOI: 10.3109/08916930903384591.
- Toll-Like Receptor and Autoimmunity.Shlomchik M, Nickerson K, Sweet R, Christensen S, Herlands R. Toll-Like Receptor and Autoimmunity. Blood 2009, 114: sci-24-sci-24. DOI: 10.1182/blood.v114.22.sci-24.sci-24.
- Differential Cytokine Production and Bystander Activation of Autoreactive B Cells in Response to CpG-A and CpG-B OligonucleotidesAvalos AM, Latz E, Mousseau B, Christensen SR, Shlomchik MJ, Lund F, Marshak-Rothstein A. Differential Cytokine Production and Bystander Activation of Autoreactive B Cells in Response to CpG-A and CpG-B Oligonucleotides The Journal Of Immunology 2009, 183: 6262-6268. PMID: 19864612, PMCID: PMC3426913, DOI: 10.4049/jimmunol.0901941.
- Murine B Cell Response to TLR7 Ligands Depends on an IFN-β Feedback LoopGreen NM, Laws A, Kiefer K, Busconi L, Kim YM, Brinkmann MM, Trail EH, Yasuda K, Christensen SR, Shlomchik MJ, Vogel S, Connor JH, Ploegh H, Eilat D, Rifkin IR, van Seventer JM, Marshak-Rothstein A. Murine B Cell Response to TLR7 Ligands Depends on an IFN-β Feedback Loop The Journal Of Immunology 2009, 183: 1569-1576. PMID: 19587008, PMCID: PMC2929820, DOI: 10.4049/jimmunol.0803899.
- Autoreactive B Cells Discriminate CpG-Rich and CpG-Poor DNA and This Response Is Modulated by IFN-αUccellini MB, Busconi L, Green NM, Busto P, Christensen SR, Shlomchik MJ, Marshak-Rothstein A, Viglianti GA. Autoreactive B Cells Discriminate CpG-Rich and CpG-Poor DNA and This Response Is Modulated by IFN-α The Journal Of Immunology 2008, 181: 5875-5884. PMID: 18941176, PMCID: PMC2584609, DOI: 10.4049/jimmunol.181.9.5875.
- Bazex syndrome (acrokeratosis paraneoplastica)Poligone B, Christensen SR, Lazova R, Heald PW. Bazex syndrome (acrokeratosis paraneoplastica) The Lancet 2007, 369: 530. PMID: 17292773, DOI: 10.1016/s0140-6736(07)60240-2.
- Toll-like Receptor 7 and TLR9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in a Murine Model of LupusChristensen SR, Shupe J, Nickerson K, Kashgarian M, Flavell RA, Shlomchik MJ. Toll-like Receptor 7 and TLR9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in a Murine Model of Lupus Immunity 2006, 25: 417-428. PMID: 16973389, DOI: 10.1016/j.immuni.2006.07.013.
- Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupusChristensen SR, Kashgarian M, Alexopoulou L, Flavell RA, Akira S, Shlomchik MJ. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus Journal Of Experimental Medicine 2005, 202: 321-331. PMID: 16027240, PMCID: PMC2212997, DOI: 10.1084/jem.20050338.