• Cancer genomics and somatic evolution
• Bayesian statistical modeling of complex biological data
• Deep learning for computational biology and medicine

Dr. Shih completed his BSc, MSc, and PhD at the University of Toronto, and he undertook postdoctoral training in the Department of Data Science at Dana-Farber Cancer Institute, with cross-appointments in the Department of Biostatistics at Harvard T.H. School of Public Health and in the Cancer Program at the Broad Institute. He also did a postdoctoral fellowship in Systems Biology at MD Anderson Cancer Institute. Prior to joining HKU, Dr. Shih was a Research Assistant Professor in the School of Biomedical Informatics at the University of Texas Health Science Center, while serving as Co-Director of the Data Science and Informatics Core for Cancer Research.

In his past research, Dr. Shih characterized the genomics of pediatric brain tumors in order to identify molecular subtypes of cancer, cancer driver genes, aberrant molecular pathways, and prognostic biomarkers. He studied the molecular evolution of brain metastases and developed novel methodologies for comparative DNA copy-number analysis. He also investigated therapeutic strategies to exploit cancer defects in DNA damage repair using pharmacogenomic data. Additionally, he also performed longitudinal studies using electronic health records and sequencing data in order to better understand cancer progression and immune response. Above all, Dr. Shih collaborates extensively with scientists and clinicians around the world.

Dr. Shih’s current research focuses on developing tailored statistical models and computational algorithms in order to derive insights from integrative genomics, high-throughput sequencing, and electronic health record data. He is particularly interested in developing statistical models that are informed by scientific knowledge and accelerated by deep learning algorithms. In this way, this framework can benefit from the rigor and interpretability of statistical models as well as the flexibility and efficiency of machine learning techniques.

We are always looking for outstanding individuals with keen interests in bioinformatics, biostatistics, or genomics research to join our lab. See lab page for more information. Potential projects include:

• Elucidating cancer somatic evolution, disease progression, and drug response by analyzing genomic data, such as
  • Characterizing poorly understood subtypes of cancer by multiple genomic modalities
  • Characterizing mutational processes across cancer types
  • Discovering cancer drivers from genome and exome sequencing data
• Developing informed Bayesian statistical models for deriving novel insights from genomic and biological data, such as
  • Discovering biologically meaningful mutational processes
  • Understanding biological processes by performing variable selection on genomic data
  • Identifying artifacts in paired-end sequencing data from FFPE samples
  • Estimating the effective reproduction number and measuring the effectiveness of interventions with causal inference
  • Extracting core signals from RNA expression data acquired on diverse platforms
• Developing probabilistic deep learning models to recognize patterns in complex biological data, such as
  • Elucidating intratumoral heterogeneity and cell-cell interactions with single-cell RNA-sequencing and spatial transcriptomics data
  • Mapping the landscape of cellular responses to drugs using contrastive learning on pharmacogenomic data

1. CNGPLD: Case-control copy-number analysis using Gaussian process latent difference.
   Shih DJH, Li RX, Müller P, Zheng WJ, Do KA, Lin SY, Carter SL.
   Bioinformatics. 2022;  38(8):2096-2101.
2. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma.
   Shih DJH*, Nayyar N*, Bihun I, Dagogo-Jack I, Aquilanti E, Bertalan M, Kaplan A, Chukwueke U, Ippen F, Alvarez-Breckenridge C, Camarda N, Lastrapes M, Kuter B, Carlos J, Gutierrez M, De Sauvage M, White M, Castro B, Hoang K, Batchelor E, Paek SH, Merrill P, Martinez-Lage Alvarez M, Berghoff AS, Gerstner ER, Batchelor T, Frosch MP, Johnson BE, Santagata S, Preusser M, Cahill DP, Carter SL, Brastianos PK.
   Nature Genetics. 2020; 52(4):371-377. *Equal contribution
3. Cytogenetic prognostication within medulloblastoma subgroups.
   Shih DJ*, Northcott PA*, Remke M*, Korshunov A, Ramaswamy V, Kool M, Luu B, Yao Y, Wang X, Dubuc AM, Garzia L, Peacock J, Mack SC, Wu X, Rolider A, Morrissy AS, Cavalli FM, Jones DT, Zitterbart K, Faria CC, Schüller U, Kren L, Kumabe T, Tominaga T, Shin Ra Y, Garami M, Hauser P, Chan JA, Robinson S, Bognár L, Klekner A, Saad AG, Liau LM, Albrecht S, Fontebasso A, Cinalli G, De Antonellis P, Zollo M, Cooper MK, Thompson RC, Bailey S, Lindsey JC, Di Rocco C, Massimi L, Michiels EM, Scherer SW, Phillips JJ, Gupta N, Fan X, Muraszko KM, Vibhakar R, Eberhart CG, Fouladi M, Lach B, Jung S, Wechsler-Reya RJ, Fèvre-Montange M, Jouvet A, Jabado N, Pollack IF, Weiss WA, Lee JY, Cho BK, Kim SK, Wang KC, Leonard JR, Rubin JB, de Torres C, Lavarino C, Mora J, Cho YJ, Tabori U, Olson JM, Gajjar A, Packer RJ, Rutkowski S, Pomeroy SL, French PJ, Kloosterhof NK, Kros JM, Van Meir EG, Clifford SC, Bourdeaut F, Delattre O, Doz FF, Hawkins CE, Malkin D, Grajkowska WA, Perek-Polnik M, Bouffet E, Rutka JT, Pfister SM, Taylor MD.
   Journal of Clinical Oncology. 2014; 32(9):886-96. *Equal contribution
4. Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
   Northcott PA*, Shih DJ*, Peacock J, Garzia L, Morrissy AS, Zichner T, Stütz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fèvre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognár L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD.
   Nature. 2012; 488(7409):49-56. *Equal contribution
5. Proteome instability is a therapeutic vulnerability in mismatch repair deficient cancer.
   McGrail DJ, Garnett J, Yin J, Dai H, Shih DJ, Nguyen T, Lam A, Li Y, Sun C, Li Y, Schmandt R, Wu JY, Hu L, Liang Y, Peng G, Jonasch E, Menter D, Yates MS , Kopetz S, Lu K, Broaddus R, Mills GB, Sahni N, Lin SY.
   Cancer Cell. 2020; 37(3):371-386.e12.
6. Intertumoral heterogeneity within medulloblastoma subgroups.
   Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri S, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Daniels C, Cho BK, Kim SK, Wang KC, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KKW, Ng HK, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhakar R, Hauser P, van Veelen MC, Kros JM, French PJ, Ra YS, Kumabe T, López-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Moore AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimentel J, Faria CC, Saad AG, Massimi L, Liau LM, Wheeler H, Nakamura H, Elbabaa SK, Perezpeña-Diazconti M, Chico Ponce de León F, Robinson S, Zapotocky M, Lassaletta A, Huang A, Hawkins CE, Tabori U, Bouffet E, Bartels U, Dirks PB, Rutka JT, Bader GD, Reimand J, Goldenberg A, Ramaswamy V, Taylor MD.
   Cancer Cell. 2017; 31(6):737-754.e6.
7. Spatial heterogeneity in medulloblastoma.
   Morrissy AS, Cavalli FMG, Remke M, Ramaswamy V, Shih DJH, Holgado BL, Farooq H, Donovan LK, Garzia L, Agnihotri S, Kiehna EN, Mercier E, Mayoh C, Papillon-Cavanagh S, Nikbakht H, Gayden T, Torchia J, Picard D, Merino DM, Vladoiu M, Luu B, Wu X, Daniels C, Horswell S, Thompson YY, Hovestadt V, Northcott PA, Jones DTW, Peacock J, Wang X, Mack SC, Reimand J, Albrecht S, Fontebasso AM, Thiessen N, Li Y, Schein JE, Lee D, Carlsen R, Mayo M, Tse K, Tam A, Dhalla N, Ally A, Chuah E, Cheng Y, Plettner P, Li HI, Corbett RD, Wong T, Long W, Loukides J, Buczkowicz P, Hawkins CE, Tabori U, Rood BR, Myseros JS, Packer RJ, Korshunov A, Lichter P, Kool M, Pfister SM, Schüller U, Dirks P, Huang A, Bouffet E, Rutka JT, Bader GD, Swanton C, Ma Y, Moore RA, Mungall AJ, Majewski J, Jones SJM, Das S, Malkin D, Jabado N, Marra MA, Taylor MD.
   Nature Genetics. 2017; 49(5):780-788.
8. Divergent clonal selection dominates medulloblastoma at recurrence.
   Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X, Skowron P, Remke M, Cavalli FM, Ramaswamy V, Lindsay PE, Jelveh S, Donovan LK, Wang X, Luu B, Zayne K, Li Y, Mayoh C, Thiessen N, Mercier E, Mungall KL, Ma Y, Tse K, Zeng T, Shumansky K, Roth AJ, Shah S, Farooq H, Kijima N, Holgado BL, Lee JJ, Matan-Lithwick S, Liu J, Mack SC, Manno A, Michealraj KA, Nor C, Peacock J, Qin L, Reimand J, Rolider A, Thompson YY, Wu X, Pugh T, Ally A, Bilenky M, Butterfield YS, Carlsen R, Cheng Y, Chuah E, Corbett RD, Dhalla N, He A, Lee D, Li HI, Long W, Mayo M, Plettner P, Qian JQ, Schein JE, Tam A, Wong T, Birol I, Zhao Y, Faria CC, Pimentel J, Nunes S, Shalaby T, Grotzer M, Pollack IF, Hamilton RL, Li XN, Bendel AE, Fults DW, Walter AW, Kumabe T, Tominaga T, Collins VP, Cho YJ, Hoffman C, Lyden D, Wisoff JH, Garvin JH Jr, Stearns DS, Massimi L, Schüller U, Sterba J, Zitterbart K, Puget S, Ayrault O, Dunn SE, Tirapelli DP, Carlotti CG, Wheeler H, Hallahan AR, Ingram W, MacDonald TJ, Olson JJ, Van Meir EG, Lee JY, Wang KC, Kim SK, Cho BK, Pietsch T, Fleischhack G, Tippelt S, Ra YS, Bailey S, Lindsey JC, Clifford SC, Eberhart CG, Cooper MK, Packer RJ, Massimino M, Garre ML, Bartels U, Tabori U, Hawkins CE, Dirks P, Bouffet E, Rutka JT, Wechsler-Reya RJ, Weiss WA, Collier LS, Dupuy AJ, Korshunov A, Jones DT, Kool M, Northcott PA, Pfister SM, Largaespada DA, Mungall AJ, Moore RA, Jabado N, Bader GD, Jones SJ, Malkin D, Marra MA, Taylor MD.
   Nature. 2016; 529(7586):351-7.
9. The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog-driven medulloblastoma.
   He X, Zhang L, Chen Y, Remke M, Shih D, Lu F, Wang H, Deng Y, Yu Y, Xia Y, Wu X, Ramaswamy V, Hu T, Wang F, Zhou W, Burns DK, Kim SH, Kool M, Pfister SM, Weinstein LS, Pomeroy SL, Gilbertson RJ, Rubin JB, Hou Y, Wechsler-Reya R, Taylor MD, Lu QR.
   Nature Medicine. 2014; 20(9):1035-42.
10. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
    Northcott PA, Lee C, Zichner T, Stütz AM, Erkek S, Kawauchi D, Shih DJ, Hovestadt V, Zapatka M, Sturm D, Jones DT, Kool M, Remke M, Cavalli FM, Zuyderduyn S, Bader GD, VandenBerg S, Esparza LA, Ryzhova M, Wang W, Wittmann A, Stark S, Sieber L, Seker-Cin H, Linke L, Kratochwil F, Jäger N, Buchhalter I, Imbusch CD, Zipprich G, Raeder B, Schmidt S, Diessl N, Wolf S, Wiemann S, Brors B, Lawerenz C, Eils J, Warnatz HJ, Risch T, Yaspo ML, Weber UD, Bartholomae CC, von Kalle C, Turányi E, Hauser P, Sanden E, Darabi A, Siesjö P, Sterba J, Zitterbart K, Sumerauer D, van Sluis P, Versteeg R, Volckmann R, Koster J, Schuhmann MU, Ebinger M, Grimes HL, Robinson GW, Gajjar A, Mynarek M, von Hoff K, Rutkowski S, Pietsch T, Scheurlen W, Felsberg J, Reifenberger G, Kulozik AE, von Deimling A, Witt O, Eils R, Gilbertson RJ, Korshunov A, Taylor MD, Lichter P, Korbel JO, Wechsler-Reya RJ, Pfister SM.
    Nature. 2014; 511(7510):428-34.
11. Notch1-induced brain tumor models the sonic hedgehog subgroup of human medulloblastoma.
    Natarajan S, Li Y, Miller EE, Shih DJ, Taylor MD, Stearns TM, Bronson RT, Ackerman SL, Yoon JK, Yun K.
    Cancer Research. 2013; 73(17):5381-90.
12. Subgroup specific prognostic implications of TP53 mutation in medulloblastoma.
    Zhukova N, Ramaswamy V_, Remke M, Pfaff E, Shih DJH, Martin DC, Castelo-Branco P, Baskin B, Ray PN, Bouffet E, von Bueren A, Pfaff E, Korshunov A, Jones DTW, Northcott PA, Kool M, Pugh T, Pomeroy SL, Cho Y, Pietsch T, Gessi M, Rutkowski S, Bogntr L, Klekner A, Cho B, Kim S, Wang K, Eberhart CG, Fevre-Montange M, Fouladi M, French PJ, Kros M, Grajkowska WA, Gupta N, Weiss WA, Hauser P, Jabado N, Jouvet A, Jung S, Kumabe T, Lach B, Leonard JR, Rubin JB, Liau LM, Massimi L, Pollack IF, Ra YS, van Meir EG, Zitterbart K, Schüller U, Hill RM, Lindsey JC, Schwalbe EC, Bailey S, Ellison D, Hawkins C, Malkin D, Clifford S, Pfister S, Taylor MD, Tabori U.
    Journal of Clinical Oncology. 2013; 31(23):2927-35.
13. Clonal selection drives genetic divergence of metastatic medulloblastoma
    Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ, Witt H, Croul S, Bouffet E, Fults DW, Eberhart CG, Garzia L, Van Meter T, Zagzag D, Jabado N, Schwartzentruber J, Majewski J, Scheetz TE, Pfister SM, Korshunov A, Li XN, Scherer SW, Cho YJ, Akagi K, MacDonald TJ, Koster J, McCabe MG, Sarver AL, Collins VP, Weiss WA, Largaespada DA, Collier LS, Taylor MD.
    Nature. 2012; 482(7386):529-33.
14. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations.
    Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino DM, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker FG, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO.
    Cell. 2012; 148(1-2):59-71.
15. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples.
    Northcott PA, Shih DJ, Remke M, Cho YJ, Kool M, Hawkins C, Eberhart CG, Dubuc A, Guettouche T, Cardentey Y, Bouffet E, Pomeroy SL, Marra M, Malkin D, Rutka JT, Korshunov A, Pfister S, Taylor MD.
    Acta Neuropathologica. 2012; 123(4):615-26.
16. Frequent amplification of a chr19q13.41 microRNA polycistron (C19MC) in aggressive PNETs.
    Li M, Lee KF, Lu Y, Clarke I, Shih D, Eberhart C, Collins VP, Van Meter T, Picard D, Zhou L, Boutros PC, Modena P, Liang ML, Scherer S, Bouffet E, Rutka JT, Pomeroy S, Lau C, Taylor MD, Gajjar A, Dirks PB, Hawkins CE, Huang A.
    Cancer Cell. 2009; 16:533-546.