Hwang, William, MD, PhD

Assistant Professor

Associated Scientist, Broad Institute of MIT and Harvard

Phone: 617-726-6906
Email: whwang1@mgh.harvard.edu
Lab: Hwang, William

Dr. Hwang is Assistant Professor of Radiation Oncology at Harvard Medical School, Principal Investigator of the Laboratory for Spatial and Systems Oncology (LaSSO) at the Center for Systems Biology and Center for Cancer Research, Attending Physician in the Department of Radiation Oncology Gastrointestinal Service at Massachusetts General Hospital, and Associated Scientist at the Broad Institute of MIT and Harvard. Dr. Hwang has had a long-standing interest in the immense temporal and spatial heterogeneity of biological systems and the many insights that can only be gleaned by studying systems at the level of their individual components—single molecules or cells. His work has been honored with numerous awards including the Rhodes Scholarship, P.D. Soros Fellowship for New Americans, Martha Gray Prize for Excellence in Research, Seidman Prize for Outstanding Thesis, summa cum laude honors from Harvard Medical School, MGH Clinical Research Award, William Shipley Research Award, ASCO/CCF Young Investigator Award, AACR NextGen Star, and Burroughs Wellcome Fund Career Award for Medical Scientists.

The Hwang lab is focused on studying tumor-stroma interactions at unprecedented resolution through the development and application of techniques in single-cell and spatial biology, multiplexed imaging, and functional genetic screens to patient-derived specimens, organoids, and mouse models to elucidate mechanisms of (1) therapeutic resistance mediated by genetic, epigenetic, and phenotypic factors including cell state plasticity; (2) treatment-mediated remodeling of the spatial microarchitecture of tumors and underlying cancer cell-stromal interactions; and (3) tumor-nerve crosstalk, which plays a critical role in the pathophysiology and morbidity of many malignancies but remains understudied.

Publications

  • Hwang WL, Su J, Shiau C, Wang PL, Guo JA, Lester NA, Barth JL, Hoffman HI, Aguirre A, Hong TS, Wo JY, Ting D, Zheng L, Mino-Kenudson M, Jacks T Molecular Mechanisms of Intratumoral Nerve Recruitment and Perineural Invasion Elucidated with Spatial Transcriptomics and CRISPR Activation. Int J Radiat Oncol Biol Phys. 2023;117(2S):S21 - PMID: 37784453 - DOI: 10.1016/j.ijrobp.2023.06.244

  • Shiau C, Cao J, Gregory MT, Gong D, Yin X, Cho JW, Wang PL, Su J, Wang S, Reeves JW, Kim TK, Kim Y, Guo JA, Lester NA, Schurman N, Barth JL, Weissleder R, Jacks T, Qadan M, Hong TS, Wo JY, Roberts H, Beechem JM, Fernandez-Del Castillo C, Mino-Kenudson M, Ting DT, Hemberg M, Hwang WL Therapy-associated remodeling of pancreatic cancer revealed by single-cell spatial transcriptomics and optimal transport analysis. bioRxiv. 2023;:ePub - PMID: 37425692 - PMCID: PMC10327107 - DOI: 10.1101/2023.06.28.546848

  • Cephas AT, Hwang WL, Maitra A, Parnas O, DelGiorno KE It is better to light a candle than to curse the darkness: single-cell transcriptomics sheds new light on pancreas biology and disease. Gut. 2023;72(6):1211-1219 - PMID: 36997301 - DOI: 10.1136/gutjnl-2022-329313

  • Bianchi A, De Castro Silva I, Deshpande NU, Singh S, Mehra S, Garrido VT, Guo X, Nivelo LA, Kolonias DS, Saigh SJ, Wieder E, Rafie CI, Dosch AR, Zhou Z, Umland O, Amirian H, Ogobuiro IC, Zhang J, Ban Y, Shiau C, Nagathihalli NS, Montgomery EA, Hwang WL, Brambilla R, Komanduri K, Villarino AV, Toska E, Stanger BZ, Gabrilovich DI, Merchant NB, Datta J Cell-autonomous Cxcl1 sustains tolerogenic circuitries and stromal inflammation via neutrophil-derived TNF in pancreatic cancer. Cancer Discov. 2023;13(6):1428-1453 - PMID: 36946782 - PMCID: PMC10259764 - DOI: 10.1158/2159-8290.CD-22-1046

  • Shiau C, Su J, Guo JA, Hong TS, Wo JY, Jagadeesh KA, Hwang WL Treatment-associated remodeling of the pancreatic cancer endothelium at single-cell resolution. Front Oncol. 2022;12:929950 - PMID: 36185212 - PMCID: PMC9524152 - DOI: 10.3389/fonc.2022.929950

  • Seldon CS, Meiyappan K, Hoffman H, Guo JA, Goel N, Hwang WL, Nguyen PL, Mahal BA, Alshalalfa M Genomic alterations predictive of poor clinical outcomes in pan-cancer. Oncotarget. 2022;13:1069-1077 - PMID: 36187555 - PMCID: PMC9518688 - DOI: 10.18632/oncotarget.28276

  • Hwang WL, Jagadeesh KA, Guo JA, Hoffman HI, Yadollahpour P, Reeves JW, Mohan R, Drokhlyansky E, Van Wittenberghe N, Ashenberg O, Farhi SL, Schapiro D, Divakar P, Miller E, Zollinger DR, Eng G, Schenkel JM, Su J, Shiau C, Yu P, Freed-Pastor WA, Abbondanza D, Mehta A, Gould J, Lambden C, Porter CBM, Tsankov A, Dionne D, Waldman J, Cuoco MS, Nguyen L, Delorey T, Phillips D, Barth JL, Kem M, Rodrigues C, Ciprani D, Roldan J, Zelga P, Jorgji V, Chen JH, Ely Z, Zhao D, Fuhrman K, Fropf R, Beechem JM, Loeffler JS, Ryan DP, Weekes CD, Ferrone CR, Qadan M, Aryee MJ, Jain RK, Neuberg DS, Wo JY, Hong TS, Xavier R, Aguirre AJ, Rozenblatt-Rosen O, Mino-Kenudson M, Castillo CF, Liss AS, Ting DT, Jacks T, Regev A Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment. Nat Genet. 2022;54(8):1178-1191 - PMID: 35902743 - PMCID: PMC10290535 - DOI: 10.1038/s41588-022-01134-8 - Cover

  • Shi DD, Guo JA, Hoffman HI, Su J, Mino-Kenudson M, Barth JL, Schenkel JM, Loeffler JS, Shih HA, Hong TS, Wo JY, Aguirre AJ, Jacks T, Zheng L, Wen PY, Wang TC, Hwang WL Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities. Lancet Oncol. 2022;23(2):e62-e74 - PMID: 35114133 - PMCID: PMC9516432 - DOI: 10.1016/S1470-2045(21)00596-9

  • Guo JA, Alshalalfa M, Kim DY, Hoffman HI, Shiau C, Su J, Hwang WL, Mahal BA DNA repair and immune checkpoint blockade response. Cancer Genet. 2022;264-265:1-4 - PMID: 35245846 - DOI: 10.1016/j.cancergen.2022.02.007

  • Ozturk H, Cingoz H, Tufan T, Yang J, Adair SJ, Tummala KS, Kuscu C, Kinali M, Comertpay G, Nagdas S, Goudreau BJ, Luleyap HU, Bingul Y, Ware TB, Hwang WL, Hsu KL, Kashatus DF, Ting DT, Chandel NS, Bardeesy N, Bauer TW, Adli M ISL2 is a putative tumor suppressor whose epigenetic silencing reprograms the metabolism of pancreatic cancer. Dev Cell. 2022;57(11):1331-1346.e9 - PMID: 35508175 - DOI: 10.1016/j.devcel.2022.04.014

  • Guo JA, Hoffman HI, Shroff SG, Chen P, Hwang PG, Kim DY, Kim DW, Cheng SW, Zhao D, Mahal BA, Alshalalfa M, Niemierko A, Wo JY, Loeffler JS, Fernandez-Del Castillo C, Jacks T, Aguirre AJ, Hong TS, Mino-Kenudson M, Hwang WL Pan-cancer Transcriptomic Predictors of Perineural Invasion Improve Occult Histopathologic Detection. Clin Cancer Res. 2021;27(10):2807-2815 - PMID: 33632928 - PMCID: PMC8127360 - DOI: 10.1158/1078-0432.CCR-20-4382

  • Guo JA, Hoffman HI, Weekes CD, Zheng L, Ting DT, Hwang WL Refining the Molecular Framework for Pancreatic Cancer with Single-cell and Spatial Technologies. Clin Cancer Res. 2021;27(14):3825-3833 - PMID: 33653818 - PMCID: PMC8282742 - DOI: 10.1158/1078-0432.CCR-20-4712

  • Freed-Pastor WA, Lambert LJ, Ely ZA, Pattada NB, Bhutkar A, Eng G, Mercer KL, Garcia AP, Lin L, Rideout WM, Hwang WL, Schenkel JM, Jaeger AM, Bronson RT, Westcott PMK, Hether TD, Divakar P, Reeves JW, Deshpande V, Delorey T, Phillips D, Yilmaz OH, Regev A, Jacks T The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer. Cancer Cell. 2021;39(10):1342-1360.e14 - PMID: 34358448 - PMCID: PMC8511341 - DOI: 10.1016/j.ccell.2021.07.007

  • Schenkel JM, Herbst RH, Canner D, Li A, Hillman M, Shanahan SL, Gibbons G, Smith OC, Kim JY, Westcott P, Hwang WL, Freed-Pastor WA, Eng G, Cuoco MS, Rogers P, Park JK, Burger ML, Rozenblatt-Rosen O, Cong L, Pauken KE, Regev A, Jacks T Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes. Immunity. 2021;54(10):2338-2353.e6 - PMID: 34534439 - PMCID: PMC8604155 - DOI: 10.1016/j.immuni.2021.08.026

  • Burger ML, Cruz AM, Crossland GE, Gaglia G, Ritch CC, Blatt SE, Bhutkar A, Canner D, Kienka T, Tavana SZ, Barandiaran AL, Garmilla A, Schenkel JM, Hillman M, de Los Rios Kobara I, Li A, Jaeger AM, Hwang WL, Westcott PMK, Manos MP, Holovatska MM, Hodi FS, Regev A, Santagata S, Jacks T Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors. Cell. 2021;184(19):4996-5014.e26 - PMID: 34534464 - PMCID: PMC8522630 - DOI: 10.1016/j.cell.2021.08.020

  • Swami N, Hwang WL, Guo JA, Hoffman H, Abramowitz MC, Elbakouny Z, Beltran H, Chipidza F, Choueiri T, Pra AD, Huang F, Kaochar S, Kantoff P, Kim DW, Kishan AU, Kobetz E, Marinac C, Mucci LA, Muralidhar V, Pollack A, Sanford NN, Schaeffer EM, Spratt DE, Zhao SG, Rebbeck TR, Nguyen PL, Feng FY, Mahal BA, Alshalalfa M Novel genomic signature predictive of response to immune checkpoint blockade: A pan-cancer analysis from project Genomics Evidence Neo-plasia Information Exchange (GENIE). Cancer Genet. 2021;258-259:61-68 - PMID: 34551377 - DOI: 10.1016/j.cancergen.2021.08.004

  • Hwang WL, Jagadeesh KA, Guo JA, Hoffman HI, Yadollahpour P, Mohan R, Drokhlyansky E, Van Wittenberghe N, Ashenberg O, Farhi S, Schapiro D, Reeves J, Zollinger DR, Eng G, Schenkel JM, Freed-Pastor WA, Rodrigues C, Gould J, Lambden C, Porter C, Tsankov A, Dionne D, Abbondanza D, Waldman J, Cuoco M, Nguyen L, Delorey T, Phillips D, Ciprani D, Kern M, Mehta A, Fuhrman K, Fropf R, Beechem J, Loeffler JS, Ryan DP, Weekes CD, Ting DT, Ferrone CR, Wo JY, Hong TS, Aguirre AJ, Rozenblatt-Rosen O, Mino-Kenudson M, Fernandez-del Castillo C, Liss AS, Jacks TE, Regev A Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatment. bioRxiv. 2020;:ePub - DOI: 10.1101/2020.08.25.267336

  • Pike LRG, Royce TJ, Mahal AR, Kim DW, Hwang WL, Mahal BA, Sanford NN Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status. J Natl Compr Canc Netw. 2020;18(2):177-184 - PMID: 32023531 - PMCID: PMC7384230 - DOI: 10.6004/jnccn.2019.7356

  • Kim DW, Buzurovic IM, Mahal BV, Hwang W, Oladeru OT, O'Farrell DA, Harris TC, Margalit DN, Lam M, Devlin PM Combined interstitial and surface high-dose-rate brachytherapy treatment of squamous cell carcinoma of the hand. J Contemp Brachytherapy. 2020;12(1):48-52 - PMID: 32190070 - PMCID: PMC7073341 - DOI: 10.5114/jcb.2020.92408

  • Lebow ES, Hwang WL, Zieminski S, Wang Y, Niemierko A, Mehan WA, Oh KS, Khandekar M, Willers H, Shih HA Early experience with hippocampal avoidance whole brain radiation therapy and simultaneous integrated boost for brain metastases. J Neurooncol. 2020;148(1):81-88 - PMID: 32307637 - DOI: 10.1007/s11060-020-03491-y

  • Hoffman HI, Guo JA, Hawkins MA, Bridgewater JA, Wo JY, Hong TS, Hwang WL Silver Linings: An Opportunity to Improve Clinical Paradigms After the COVID-19 Pandemic. JCO Oncol Pract. 2020;16(9):532-534 - PMID: 32469687 - DOI: 10.1200/OP.20.00335

  • Grossberg AJ, Chu LC, Deig CR, Fishman EK, Hwang WL, Maitra A, Marks DL, Mehta A, Nabavizadeh N, Simeone DM, Weekes CD, Thomas CR Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma. CA Cancer J Clin. 2020;70(5):375-403 - PMID: 32683683 - PMCID: PMC7722002 - DOI: 10.3322/caac.21626

  • Mehta A, Hwang WL, Weekes C The present and future of systemic and microenvironment-targeted therapy for pancreatic adenocarcinoma. Ann Pancreat Cancer. 2020;3:ePub - PMID: 33294843 - PMCID: PMC7720884 - DOI: 10.21037/apc-2020-pda-05

  • Hwang WL, Wolfson RL, Niemierko A, Marcus KJ, DuBois SG, Haas-Kogan D Clinical Impact of Tumor Mutational Burden in Neuroblastoma. J Natl Cancer Inst. 2019;111(7):695-699 - PMID: 30307503 - PMCID: PMC6624164 - DOI: 10.1093/jnci/djy157

  • Liu KX, Lamba N, Hwang WL, Niemierko A, DuBois SG, Haas-Kogan DA Risk stratification by somatic mutation burden in Ewing sarcoma. Cancer. 2019;125(8):1357-1364 - PMID: 30602061 - DOI: 10.1002/cncr.31919

  • Sanford NN, Hwang WL, Pike LRG, Lam AC, Royce TJ, Mahal BA Trimodality therapy for HPV-positive oropharyngeal cancer: A population-based study: Trimodality therapy for HPV+ OPC. Oral Oncol. 2019;98:28-34 - PMID: 31536843 - PMCID: PMC7358785 - DOI: 10.1016/j.oraloncology.2019.09.009

  • Niyazi M, Niemierko A, Paganetti H, Söhn M, Schapira E, Goldberg S, Adams J, Kim V, Oh KS, Hwang WL, Lu HM, Belka C, Busse PM, Loeffler JS, Shih HA Volumetric and actuarial analysis of brain necrosis in proton therapy using a novel mixture cure model. Radiother Oncol. 2019;142:154-161 - PMID: 31563411 - DOI: 10.1016/j.radonc.2019.09.008

  • Lamba N, Hwang WL, Kim DW, Niemierko A, Marciscano AE, Mehan WA, Benayoun MD, Curry WT, Barker FG, Martuza RL, Dunn IF, Claus E, Bi WL, Aizer AA, Alexander BM, Oh KS, Loeffler JS, Shih HA Atypical Histopathological Features and the Risk of Treatment Failure in Nonmalignant Meningiomas: A Multi-Institutional Analysis. World Neurosurg. 2019;133:e804-e812 - PMID: 31605839 - DOI: 10.1016/j.wneu.2019.10.002

  • Hwang WL, Niemierko A, Hwang KL, Hubbeling H, Schapira E, Gainor JF, Keane FK Clinical Outcomes in Patients With Metastatic Lung Cancer Treated With PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy. JAMA Oncol. 2018;4(2):253-255 - PMID: 28973343 - PMCID: PMC5838581 - DOI: 10.1001/jamaoncol.2017.3808

  • Hwang WL, Pleskow HM, Miyamoto DT Molecular analysis of circulating tumors cells: Biomarkers beyond enumeration. Adv Drug Deliv Rev. 2018;125:122-131 - PMID: 29326053 - DOI: 10.1016/j.addr.2018.01.003

  • Hwang WL, Tendulkar RD, Niemierko A, Agrawal S, Stephans KL, Spratt DE, Hearn JW, Koontz BF, Lee WR, Michalski JM, Pisansky TM, Liauw SL, Abramowitz MC, Pollack A, Moghanaki D, Anscher MS, Den RB, Zietman AL, Stephenson AJ, Efstathiou JA Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features. JAMA Oncol. 2018;4(5):e175230 - PMID: 29372236 - PMCID: PMC5885162 - DOI: 10.1001/jamaoncol.2017.5230

  • Hwang WL, Pike LRG, Royce TJ, Mahal BA, Loeffler JS Safety of combining radiotherapy with immune-checkpoint inhibition. Nat Rev Clin Oncol. 2018;15(8):477-494 - PMID: 29872177 - DOI: 10.1038/s41571-018-0046-7

  • Sanford NN, Mahal BA, Royce TJ, Pike LRG, Hwang WL Sex Disparity and Copy Number Alterations in Esophageal Squamous Cell Carcinoma. Clin Gastroenterol Hepatol. 2018;17(6):1207-1209 - PMID: 30120994 - DOI: 10.1016/j.cgh.2018.08.026

  • Pike LRG, Hwang WL, Royce TJ, Sanford NN, Mahal BA HPV status predicts for improved survival following chemotherapy in metastatic squamous cell carcinoma of the oropharynx. Oral Oncol. 2018;86:69-74 - PMID: 30409322 - DOI: 10.1016/j.oraloncology.2018.09.007

  • Hwang WL, Niemierko A, Efstathiou JA Comparing Adjuvant vs Early-Salvage Radiotherapy After Radical Prostatectomy-Reply. JAMA Oncol. 2018;4(11):1620-1621 - PMID: 30422248 - DOI: 10.1001/jamaoncol.2018.3552

  • Kim D, Niemierko A, Hwang WL, Stemmer-Rachamimov AO, Curry WT, Barker FG, Martuza RL, Oh KS, Loeffler JS, Shih HA Histopathological prognostic factors of recurrence following definitive therapy for atypical and malignant meningiomas. J Neurosurg. 2017;128(4):1123-1132 - PMID: 28621619 - DOI: 10.3171/2016.11.JNS16913

  • Hwang KL, Hwang WL, Bussière MR, Shih HA The role of radiotherapy in the management of high-grade meningiomas. Chin Clin Oncol. 2017;6(Suppl 1):S5 - PMID: 28758409 - DOI: 10.21037/cco.2017.06.09

  • Harada BT, Hwang WL, Deindl S, Chatterjee N, Bartholomew B, Zhuang X Stepwise nucleosome translocation by RSC remodeling complexes. eLife. 2016;5:ePub - PMID: 26895087 - PMCID: PMC4769157 - DOI: 10.7554/eLife.10051

  • Hwang WL, Hwang KL, Miyamoto DT The promise of circulating tumor cells for precision cancer therapy. Biomark Med. 2016;10(12):1269-1285 - PMID: 27924634 - PMCID: PMC5827810 - DOI: 10.2217/bmm-2016-0192

  • Hwang WL, Marciscano AE, Niemierko A, Kim DW, Stemmer-Rachamimov AO, Curry WT, Barker FG, Martuza RL, Loeffler JS, Oh KS, Shih HA, Larvie M Imaging and extent of surgical resection predict risk of meningioma recurrence better than WHO histopathological grade. Neuro Oncol. 2015;18(6):863-72 - PMID: 26597949 - PMCID: PMC4864259 - DOI: 10.1093/neuonc/nov285

  • Hwang WL, Deindl S, Harada BT, Zhuang X Histone H4 tail mediates allosteric regulation of nucleosome remodelling by linker DNA. Nature. 2014;512(7513):213-7 - PMID: 25043036 - PMCID: PMC4134374 - DOI: 10.1038/nature13380

  • Deindl S, Hwang WL, Hota SK, Blosser TR, Prasad P, Bartholomew B, Zhuang X ISWI remodelers slide nucleosomes with coordinated multi-base-pair entry steps and single-base-pair exit steps. Cell. 2013;152(3):442-52 - PMID: 23374341 - PMCID: PMC3647478 - DOI: 10.1016/j.cell.2012.12.040

  • Maglia G, Heron AJ, Hwang WL, Holden MA, Mikhailova E, Li Q, Cheley S, Bayley H Droplet networks with incorporated protein diodes show collective properties. Nat Nanotechnol. 2009;4(7):437-40 - PMID: 19581896 - DOI: 10.1038/nnano.2009.121

  • Hwang WL, Chen M, Cronin B, Holden MA, Bayley H Asymmetric droplet interface bilayers. J Am Chem Soc. 2008;130(18):5878-9 - PMID: 18407631 - DOI: 10.1021/ja802089s

  • Syeda R, Holden MA, Hwang WL, Bayley H Screening blockers against a potassium channel with a droplet interface bilayer array. J Am Chem Soc. 2008;130(46):15543-8 - PMID: 18950170 - DOI: 10.1021/ja804968g

  • Xu T, Hwang WL, Su F, Chakrabarty K. Automated design of pin-constrained digital microfluidic biochips under droplet-interference constraints. Journal on Emerging Technologies in Computing. 2007;3(3):14

  • Su F, Hwang WL, Mukherjee A, Chakrabarty K Testing and diagnosis of realistic defects in digital microfluidic biochips. Journal of Electronic Testing. 2007;23(2-3):219-33

  • Hwang WL, Holden MA, White S, Bayley H Electrical behavior of droplet interface bilayer networks: experimental analysis and modeling. J Am Chem Soc. 2007;129(38):11854-64 - PMID: 17764183 - DOI: 10.1021/ja074071a

  • Curry A, Hwang WL, Wax A Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture. Opt Express. 2006;14(14):6535-42 - PMID: 19516830 - DOI: 10.1364/oe.14.006535

  • Szu H, Hwang WL Self-supervised backpropagation in stem cells. IEEE Connections. 2003;1(3):8-9