Research & Clinical Summary

Our laboratory investigates the mechanisms through which cancer-mutated genes drive tumorigenesis. We focus on small cell lung carcinoma (SCLC), which is a deadly neuroendocrine cancer type.  We employ genetically engineered mouse models, patient derived xenograft models and functional screens, performed in cell culture and in vivo, to understand how specific genetic alterations promote SCLC and influence response to therapies. One major area of interest is in how chromatin regulating genes, which are frequently mutated in SCLC, drive tumorigenesis. A second major area of interest is in understanding why SCLC is initially so sensitive to chemotherapy but rapidly becomes chemoresistant.  We also try to identify vulnerabilities in subsets of SCLC using functional screens that can provide novel drug targets for SCLC that we can then study using in vivo models.

Interests: Cancer, Cell Signaling, Genetic Disease, Genomics

Publications

The following publications were retrieved from PubMed:

Wu N, Jia D, Bates B, Basom R, Eberhart CG, MacPherson D,
“A mouse model of MYCN-driven retinoblastoma reveals MYCN-independent tumor reemergence.”
The Journal of clinical investigation 127.3 (2017 Mar 1): 888-898.

Rice N, Srinivasan B, Macpherson D,
“Case Report: Metastatic Infratemporal Soft Tissue Myeloma Presenting as a Numb Lower Lip.”
Dental update 44.1 (2017 Jan): 53-4.

Jia D, Augert A, Kim DW, Eastwood E, Wu N, Ibrahim AH, Kim KB, Dunn CT, Pillai SPS, Gazdar AF, Bolouri H, Park KS, MacPherson D,
“Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition.”
Cancer discovery 8.11 (2018 Nov): 1422-1437.

Augert A, Eastwood E, Ibrahim AH, Wu N, Grunblatt E, Basom R, Liggitt D, Eaton KD, Martins R, Poirier JT, Rudin CM, Milletti F, Cheng WY, Mack F, MacPherson D,
“Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition.”
Science signaling 12.567 (2019 Feb 5): .

Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, Heymach JV, Johnson JE, Lehman JM, MacPherson D, Massion PP, Minna JD, Oliver TG, Quaranta V, Sage J, Thomas RK, Vakoc CR, Gazdar AF,
“Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data.”
Nature reviews. Cancer 19.5 (2019 May): 289-297.

Hiatt JB, MacPherson D,
“Delivering a STINGing Blow to Small Cell Lung Cancer via Synergistic Inhibition of DNA-Damage Response and Immune-Checkpoint Pathways.”
Cancer discovery 9.5 (2019 May): 584-586.

Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, Heymach JV, Johnson JE, Lehman JM, MacPherson D, Massion PP, Minna JD, Oliver TG, Quaranta V, Sage J, Thomas RK, Vakoc CR, Gazdar AF,
“Author Correction: Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data.”
Nature reviews. Cancer 19.7 (2019 Jul): 415.

Corella AN, Cabiliza Ordonio MVA, Coleman I, Lucas JM, Kaipainen A, Nguyen HM, Sondheim D, Brown LG, True LD, Lee JK, MacPherson D, Nghiem P, Gulati R, Morrissey C, Corey E, Nelson PS,
“Identification of Therapeutic Vulnerabilities in Small-cell Neuroendocrine Prostate Cancer.”
Clinical cancer research : an official journal of the American Association for Cancer Research 26.7 (2020 Apr 1): 1667-1677.

Poirier JT, George J, Owonikoko TK, Berns A, Brambilla E, Byers LA, Carbone D, Chen HJ, Christensen CL, Dive C, Farago AF, Govindan R, Hann C, Hellmann MD, Horn L, Johnson JE, Ju YS, Kang S, Krasnow M, Lee J, Lee SH, Lehman J, Lok B, Lovly C, MacPherson D, McFadden D, Minna J, Oser M, Park K, Park KS, Pommier Y, Quaranta V, Ready N, Sage J, Scagliotti G, Sos ML, Sutherland KD, Travis WD, Vakoc CR, Wait SJ, Wistuba I, Wong KK, Zhang H, Daigneault J, Wiens J, Rudin CM, Oliver TG,
“New Approaches to SCLC Therapy: From the Laboratory to the Clinic.”
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 15.4 (2020 Apr): 520-540.

Augert A, Mathsyaraja H, Ibrahim AH, Freie B, Geuenich MJ, Cheng PF, Alibeckoff SP, Wu N, Hiatt JB, Basom R, Gazdar A, Sullivan LB, Eisenman RN, MacPherson D,
“MAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer.”
Cancer cell 38.1 (2020 Jul 13): 97-114.e7.

Grunblatt E, Wu N, Zhang H, Liu X, Norton JP, Ohol Y, Leger P, Hiatt JB, Eastwood EC, Thomas R, Ibrahim AH, Jia D, Basom R, Eaton KD, Martins R, Houghton AM, MacPherson D,
“MYCN drives chemoresistance in small cell lung cancer while USP7 inhibition can restore chemosensitivity.”
Genes & development 34.17-18 (2020 Sep 1): 1210-1226.

Witty DR, Alvaro G, Derjean D, Giblin GMP, Gunn K, Large C, Macpherson DT, Morisset V, Owen D, Palmer J, Rugiero F, Tate S, Hinckley CA, Naik H,
“Discovery of Vixotrigine: A Novel Use-Dependent Sodium Channel Blocker for the Treatment of Trigeminal Neuralgia.”
ACS medicinal chemistry letters 11.9 (2020 Sep 10): 1678-1687.

Norton JP, Augert A, Eastwood E, Basom R, Rudin CM, MacPherson D,
“Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas.”
Genes & development 35.11-12 (2021 Jun): 870-887.

Burkitt KH, Rodriguez KL, Mor MK, Fine MJ, Clark WJ, Macpherson DS, Mannozzi CM, Muldoon MF, Long JA, Hausmann LRM,
“Evaluation of a collaborative VA network initiative to reduce racial disparities in blood pressure control among veterans with severe hypertension.”
Healthcare (Amsterdam, Netherlands) 8 Suppl 1. (2021 Jun): 100485.

Mathsyaraja H, Catchpole J, Freie B, Eastwood E, Babaeva E, Geuenich M, Cheng PF, Ayers J, Yu M, Wu N, Moorthi S, Poudel KR, Koehne A, Grady W, Houghton AM, Berger AH, Shiio Y, MacPherson D, Eisenman RN,
“Loss of MGA repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness.”
eLife 10. (2021 Jul 8): .