Philip Scumpia*

/in /by


Philip Scumpia, Ph.D.

Office Address:
924 Westwood Blvd., Suite 730

Affiliations

Assistant Professor-in-Residence, Medicine-Dermatology
Research Interests

My overarching research goal is to develop a better understanding of how the immune system contributes to cutaneous health and disease and to leverage these mechanistic insights to develop new avenues for therapy. My laboratory focuses on how immune cell populations integrate molecular and environmental signals from the cutaneous microenvironment to provide protection against cancer, infection, wounding, or autoimmune responses mistakenly trigger maladaptive immune responses during autoinflammatory/autoimmune skin diseases. This knowledge will lead to logically designed, effective therapeutic strategies to either strengthen antimicrobial and/or anti-cancer responses in the skin, enhance wound healing and/or skin regeneration, or diminish auto-inflammatory or autoimmune phenomena. My laboratory research program has three major directions:<

1. How do neural inputs modulate cutaneous immune responses? We are finding that neuroendocrine (glucocorticoids) and sympathetic (adrenergic) nervous system stimuli selectively inhibit distinct inflammatory stimuli, and endogenous glucocorticoids and beta-adrenergic stimuli suppress psoriasis in a mouse model. Our goal is to use transgenic models to better define the cell populations that utilize these neural inputs as rheostats on immune<

activation to develop more targeted therapies. We are also finding that signals from the sympathetic nervous system also are required for cutaneous regeneration after injury.<

2. How do we leverage cell to cell interactions within the cutaneous immune microenvironment to enhance wound healing, skin regeneration or cutaneous host defense? We have identified several ways to modulate cutaneous immunity in several different models. Specific projects include:<

– We have also found that a biomaterial that activates macrophages and lymphocytes type 2 immune immune responses in in the skin can directly trigger skin regeneration. What are the signals produced by these immune cells that can prevent fibrosis and activate skin regeneration.<

– We have found that cGAS-Sting activation subverts host defense against Staphylococcus aureus infection through type I IFN production, and type I IFN can also be modulated by changing lipid concentrations in the skin to enhance host resistance to bacterial toxins. We are now studying novel approaches to alter lipid composition to improve cellular defense strategies against skin pathogens.<

– We are finding that deletion of a key interferon regulatory pathway from the host microenvironment leads to enhanced growth of melanoma and other tumors implanted subcutaneously, but deletion of that interferon regulatory pathway from tumor cells themselves enhances anti-tumor immune responses. Understanding how immune factors affect tumor growth in a tumor cell-intrinsic vs tumor cell extrinsic manner will be used to improve cancer immunotherapies.<

Publications

A selected list of publications:

Biopsy-free in vivo virtual histology of skin using deep learning. Light Sci Appl. 2021 Nov 18; 10(1):233. Li J, Garfinkel J, Zhang X, Wu D, Zhang Y, de Haan K, Wang H, Liu T, Bai B, Rivenson Y, Rubinstein G, Scumpia PO, Ozcan A. PMID: 34795202; PMCID: PMC8602311.

Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects. PLoS One. 2021; 16(6):e0252597. Escuin-Ordinas H, Liu Y, Sun L, Hugo W, Dimatteo R, Huang RR, Krystofinski P, Azhdam A, Lee J, Comin-Anduix B, Cochran AJ, Lo RS, Segura T, Scumpia PO, Ribas A. PMID: 34161353; PMCID: PMC8221471.

Melanoma dedifferentiation induced by IFN-γ epigenetic remodeling in response to anti-PD-1 therapy. J Clin Invest. 2021 06 15; 131(12). Kim YJ, Sheu KM, Tsoi J, Abril-Rodriguez G, Medina E, Grasso CS, Torrejon DY, Champhekar AS, Litchfield K, Swanton C, Speiser DE, Scumpia PO, Hoffmann A, Graeber TG, Puig-Saus C, Ribas A. PMID: 33914706; PMCID: PMC8203459.

Detection of viral gene expression in risk-stratified biopsies reveals no active HPV in cutaneous squamous cell carcinoma. Exp Dermatol. 2021 11; 30(11):1711-1716. Vandiver AR, Thomas BJ, Karimzada M, Knowles BC, Botten GA, Spreafico R, Rotman JN, Gharavi NM, Chesnut C, Wesel K, Mangul S, Soriano T, Scumpia PO. PMID: 34036652; PMCID: PMC9639216.

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication. Cell Rep. 2021 04 06; 35(1):108940. Garcia G, Sharma A, Ramaiah A, Sen C, Purkayastha A, Kohn DB, Parcells MS, Beck S, Kim H, Bakowski MA, Kirkpatrick MG, Riva L, Wolff KC, Han B, Yuen C, Ulmert D, Purbey PK, Scumpia P, Beutler N, Rogers TF, Chatterjee AK, Gabriel G, Bartenschlager R, Gomperts B, Svendsen CN, Betz UAK, Damoiseaux RD, Arumugaswami V. PMID: 33784499; PMCID: PMC7969873.

Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Antitumor T-cell Immunity. Cancer Discov. 2021 03; 11(3):714-735. Hong A, Piva M, Liu S, Hugo W, Lomeli SH, Zoete V, Randolph CE, Yang Z, Wang Y, Lee JJ, Lo SJ, Sun L, Vega-Crespo A, Garcia AJ, Shackelford DB, Dubinett SM, Scumpia PO, Byrum SD, Tackett AJ, Donahue TR, Michielin O, Holmen SL, Ribas A, Moriceau G, Lo RS. PMID: 33318037; PMCID: PMC7933113.

Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing. Nat Mater. 2021 04; 20(4):560-569. Griffin DR, Archang MM, Kuan CH, Weaver WM, Weinstein JS, Feng AC, Ruccia A, Sideris E, Ragkousis V, Koh J, Plikus MV, Di Carlo D, Segura T, Scumpia PO. PMID: 33168979; PMCID: PMC8005402.

Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins. Nat Immunol. 2020 07; 21(7):746-755. Zhou QD, Chi X, Lee MS, Hsieh WY, Mkrtchyan JJ, Feng AC, He C, York AG, Bui VL, Kronenberger EB, Ferrari A, Xiao X, Daly AE, Tarling EJ, Damoiseaux R, Scumpia PO, Smale ST, Williams KJ, Tontonoz P, Bensinger SJ. PMID: 32514064; PMCID: PMC7778040.

Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome. Cell Metab. 2020 07 07; 32(1):128-143.e5. Hsieh WY, Zhou QD, York AG, Williams KJ, Scumpia PO, Kronenberger EB, Hoi XP, Su B, Chi X, Bui VL, Khialeeva E, Kaplan A, Son YM, Divakaruni AS, Sun J, Smale ST, Flavell RA, Bensinger SJ. PMID: 32516576; PMCID: PMC7891175.

ER Stress Regulates Immunosuppressive Function of Myeloid Derived Suppressor Cells in Leprosy that Can Be Overcome in the Presence of IFN-γ. iScience. 2020 May 22; 23(5):101050. Kelly-Scumpia KM, Choi A, Shirazi R, Bersabe H, Park E, Scumpia PO, Ochoa MT, Yu J, Ma F, Pellegrini M, Modlin RL. PMID: 32339990; PMCID: PMC7190750.

Collaborative interactions of heterogenous ribonucleoproteins contribute to transcriptional regulation of sterol metabolism in mice. Nat Commun. 2020 02 20; 11(1):984. Zhang Z, Feng AC, Salisbury D, Liu X, Wu X, Kim J, Lapina I, Wang D, Lee B, Fraga J, Pan C, Williams KJ, Lusis AJ, Scumpia P, Sallam T. PMID: 32080181; PMCID: PMC7033216.

Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particle Scaffolds. Small. 2019 09; 15(39):e1903147. Koh J, Griffin DR, Archang MM, Feng AC, Horn T, Margolis M, Zalazar D, Segura T, Scumpia PO, Di Carlo D. PMID: 31410986; PMCID: PMC6761037.

Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network. J Immunol. 2018 05 01; 200(9):3244-3258. Keegan C, Krutzik S, Schenk M, Scumpia PO, Lu J, Pang YLJ, Russell BS, Lim KS, Shell S, Prestwich E, Su D, Elashoff D, Hershberg RM, Bloom BR, Belisle JT, Fortune S, Dedon PC, Pellegrini M, Modlin RL. PMID: 29610140; PMCID: PMC5916334.

Publisher Correction: Elastomeric sensor surfaces for high-throughput single-cell force cytometry. Nat Biomed Eng. 2018 Apr; 2(4):265. Pushkarsky I, Tseng P, Black D, France B, Warfe L, Koziol-White CJ, Jester WF, Trinh RK, Lin J, Scumpia PO, Morrison SL, Panettieri RA, Damoiseaux R, Di Carlo D. PMID: 31015734.

Skin lesions serve as clues to relapse of pediatric blastic plasmacytoid dendritic cell neoplasm. Pediatr Dermatol. 2018 Mar; 35(2):e132-e135. Dreyer S, Mednik S, Truong A, Worswick S, Scumpia P, Neill D, Kannan S, Hogeling M. PMID: 29436012.

Elastomeric sensor surfaces for high-throughput single-cell force cytometry. Nat Biomed Eng. 2018 02; 2(2):124-137. Pushkarsky I, Tseng P, Black D, France B, Warfe L, Koziol-White CJ, Jester WF, Trinh RK, Lin J, Scumpia PO, Morrison SL, Panettieri RA, Damoiseaux R, Di Carlo D. PMID: 31015629; PMCID: PMC6619436.

Melanocyte Stem Cell Activation and Translocation Initiate Cutaneous Melanoma in Response to UV Exposure. Cell Stem Cell. 2017 Nov 02; 21(5):665-678.e6. Moon H, Donahue LR, Choi E, Scumpia PO, Lowry WE, Grenier JK, Zhu J, White AC. PMID: 29033353; PMCID: PMC9004284.

Levofloxacin-induced purpura annularis telangiectodes of Majocchi. Cutis. 2017 10; 100(4):E10-E12. Okhovat JP, Hsiao JL, Scumpia P, Yoo KY. PMID: 29136063.

Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation. Immunity. 2017 09 19; 47(3):421-434.e3. Purbey PK, Scumpia PO, Kim PJ, Tong AJ, Iwamoto KS, McBride WH, Smale ST. PMID: 28930658; PMCID: PMC5661954.

Recurrent Tumor Cell-Intrinsic and -Extrinsic Alterations during MAPKi-Induced Melanoma Regression and Early Adaptation. Cancer Discov. 2017 11; 7(11):1248-1265. Song C, Piva M, Sun L, Hong A, Moriceau G, Kong X, Zhang H, Lomeli S, Qian J, Yu CC, Damoiseaux R, Kelley MC, Dahlman KB, Scumpia PO, Sosman JA, Johnson DB, Ribas A, Hugo W, Lo RS. PMID: 28864476; PMCID: PMC6668729.