Photo of Dipanjan Chowdhury,  PhD

Dipanjan Chowdhury, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


dipanjan_chowdhury@dfci.harvard.edu

Dipanjan Chowdhury, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Radiation Oncology, Harvard Medical School
  • Professor, Radiation Oncology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Repair of Double stranded DNA breaks-pathway choices and more

Double stranded DNA breaks (DSBs) are critical for cell health as a single unrepaired DSB is sufficient for inducing apoptosis. Two major mechanistically distinct pathways, homologous recombination (HR) and non-homologous end joining (NHEJ), have evolved to deal with DSBs and are regulated by factors that are conserved from yeast to mammals. The relative contribution of the competing DSB repair pathways differ in the different cell types and in different phases of the cell cycle, and this balance is critical for maintaining genomic stability.

Interplay of DSB repair pathways during cell cycle and impact on therapy: A decisive factor in the choice between DSB repair pathways is in the competition between DNA end protection (necessary for NHEJ) and DNA end resection (necessary for HR). DSB end resection must be appropriately restricted to S/G2 phases of the cell cycle, as HR requires the presence of an intact sister chromatid. Depletion of NHEJ promoting factors such as 53BP1 allows DNA end resection in the G1 phase, thereby impairing DSB repair and causing genomic instability. Conversely, loss of the HR protein, BRCA1 (critical for initiating end resection) allows the error-prone NHEJ pathway to dominate throughout the cell cycle potentially also contributing to mutations/deletions. From the perspective of therapy, loss of BRCA1 provides a therapeutic opportunity as these tumors are exquisitely sensitive to inhibitors of the DNA repair protein, poly (ADP-ribose) polymerase (PARP), and are also susceptible to platinum-based drugs. Surprisingly, loss of 53BP1 or associated factors (RIF1, PTIP) in these tumors render them insensitive to PARP inhibitors, as DNA end resection and the subsequent steps of the HR pathway is restored.

(a) MicroRNAs in DSB repair –pathway choice and therapeutic implications: We have conducted functional screens to discover microRNA (miRNA)s that down-modulate DSB repair proteins, and influence specific repair pathways. Ectopic expression of NHEJ-regulating miRNAs in BRCA1-deficient ovarian causes resistance to PARP inhibitors and platinum-drugs. In turn these patients have poor prognosis. We now utilize focused sequencing of miRNAs from BRCA deficient tumors that are resistant to therapy to identify miRNAs that influence the DNA repair machinery. Importantly these miRNAs have significant clinical relevance as therapeutic targets or predictive biomarkers of response.

(b) Systematic identification of factors that influence the BRCA-pathway: The (CRISPR)-Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines with disrupted genes. We are utilizing the whole-genome CRISPR library to comprehensively identify factors that restore HR-mediated DSB repair in BRCA1/2-deficient ovarian tumors and make these tumors resistant to PARP inhibitors and platinum-drugs. The goal is to better understand the biology of DSB repair, cross-talk with other signaling pathways and elucidate the mechanism of chemo-resistance.

(c) Non-coding (nc) RNAs and RNA binding proteins that impact DSB repair: Using cross-linking/immunoprecipitation and RNA-Seq we now have evidence that uncharacterized non-coding RNAs may be associated with DNA repair factors such as 53BP1 and directly impact the repair process. We are investigating the precise mechanism by which these ncRNAs associate with and functionally impact DSB repair. Central to all 53BP1 activities is its recruitment to DSBs via the interaction of the tandem Tudor domain with dimethylated lysine 20 of histone H4 (H4K20me2).We have identified an uncharacterized RNA binding protein, TIRR (Tudor Interacting Repair Regulator) that directly binds the tandem Tudor domain and masks its H4K20me2 binding motif. Over-expression of TIRR impedes 53BP1 function by blocking its localization to DSBs. Depletion of TIRR destabilizes 53BP1 in the nuclear soluble fraction and also alters the DSB-induced protein complex centering 53BP1 to broadly impede repair. We continue to characterize, TIRR as a new factor that influences DNA repair.

Down-regulation of DSB repair in mitosis and activation via dephosphorylation: Interestingly in mitosis DSBs are recognized but not repaired, that is, factors like 53BP1 and BRCA1 are excluded from DSBs. Mitosis is the only phase of the cell cycle that lacks a DNA damage checkpoint.

(a) Why activating DSB repair pathways in mitosis leads to genomic instability? We have recently observed that phosphorylation of 53BP1 at specific residues during mitosis impedes its recruitment to chromatin and DSBs. Dephosphorylation via a PP4/R3beta phosphatase complex restores activity in the G1 phase. Counter-intuitively we observe that ectopic activation of the 53BP1 pathway, consequently the NHEJ pathway, in mitotic cells causes genomic instability and mitotic defects. We are addressing this question using a combination of cytological tools and single-cell sequencing.

(b) Phosphatases in DSB repair. We have demonstrated that phosphatases participate in multiple steps of the DNA damage response, which includes facilitating DNA repair in the context of the cell cycle phase, restoration of chromatin structure and regulating checkpoints. We now have evidence that dephosphorylation of specific phospho-residues of DNA repair proteins is a pre-requisite for their function. We have developed a novel phospho-proteomic strategy to identify these factors and also to identify phosphatases that regulate their activity. Our goal is to continue these studies and systematically investigate the role of phosphatases in DSB repair.

Translational Projects

Serum miRNAs as biomarkers

Of the various classes of circulating nucleic acids, miRNAs have been recently characterized, and are rapidly emerging as useful non-invasive biomarkers for various pathological conditions. Most of the published studies using circulating miRNAs as biomarkers have focused on cancer. Despite high concentration of RNAses in plasma and serum, circulating miRNAs are surprisingly stable and the levels are reproducibly consistent across individuals of the same species. Some of the key molecular properties of miRNAs include stability against external impacts such as enzymatic degradation, freezing, and thawing, or intense pH conditions. Several reports indicate that miRNAs are distinctly more stable than mRNAs and a modest number of miRNAs may be sufficient to serve as markers to differentiate a pathological condition. miRNAs are detected and quantitatively assayed via high-throughput expression analysis which is rapid, sensitive and, with multiple PCR-based strategies available, technically easy compared to other biomarkers.

Radiation and serum miRNAs: The exposure of human populations to radiation, either accidentally (e.g. nuclear plant incident) or intentionally (e.g. terrorism) poses a significant threat to public health. One of the most important steps in the medical management of a nuclear disaster is to triage individuals who are minimally exposed and do not need treatment compared to those who received a dose of radiation that has caused significant injury to internal organs and tissues. Existing biodosimetry techniques and devices do not predict the severity of injury sustained by specific organs and tissues, and thus do not allow for the prompt organ- and tissue-directed medical treatment that might be provided by any available radiation medical countermeasures. We began to address this question by identifying serum miRNAs that predict long-term radiation-induced hematopoietic injury in mice. Recently we used non-human primates (NHPs) to demonstrate that this concept is evolutionarily conserved and thus that serum miRNA signatures have the potential to serve as prediction biomarkers for radiation-induced fatality in a human population. Genomic analysis of these radiation-responsive conserved miRNAs revealed that a common transcriptional network regulates these miRNAs in human, mice, and NHPs. From the clinical perspective, peripheral blood cells from radiation-therapy patients also show radiation-induced changes in miRNA expression. We also observed that differential expression of serum miRNAs may reflect biological tumor response (or resistance) to thoracic radiation in non-small-cell-lung cancer (NSCLC) patients.

(a) Predicting Radiation Induced Mortality: In animal models we have evidence that distinct sets of serum miRNAs correlates with radiation dose, and also the time-frame after radiation exposure (that is days versus weeks). Overall the goal is to build on our preliminary studies and establish miRNA signatures that predict radiation injury to allow for timely and appropriate treatment of radiation victims.

(b) Radiation Therapy Induced Secondary Malignancy: While a frequently used and effective element of multimodality cancer treatment, radiation therapy results in toxicities to normal tissues that represent a significant public health burden. These risks are amplified in pediatric patients who survive their primary malignancy and carry a 20.5% 30-year cumulative risk of second malignancies, with a 2.7x relative risk conferred by radiation. 25 years after diagnosis, the death rate due to subsequent malignancies in these pediatric patients exceeds that due to all other causes. An urgent need thus exists for noninvasive biomarkers of second malignancy risk that can be evaluated early in the disease process, in time for potential interventions to reduce such risk. We hypothesize that miRNAs present in serum drawn soon after irradiation will predict underlying susceptibility to long-term radiation-induced cancers and identify pediatric patients at increased risk for this all-too-common consequence.

Early Detection of Ovarian cancer utilizing serum miRNAs: Ovarian cancer is one of the most lethal malignant gynecological tumors. Its incidence rate ranks the second among malignant tumors of the genital system following uterine corpus cancer, but its mortality rate was the highest. Given that ovarian cancer is located deep within the pelvis and is difficult to touch, as well as the lack of typical early symptoms and effective diagnostic methods, more than 70% of patients are diagnosed at advanced stage. At this stage, the tumor has metastasized into the peritoneal cavity or to distant locations which significantly limits the efficacy of therapy. Although surgical treatment and chemotherapy of ovarian cancer have improved in recent years, the prognosis of ovarian cancer remains poor. The five-year survival rate for all stages of ovarian cancer is 47%. However, for cases where a diagnosis of the disease is made early, when the cancer is still confined to the primary site, the five-year survival rate is 92.7%. Hence, there is a great need for identification of novel non-invasive biomarkers for early tumor detection. Our initial analysis indicates that a miRNA signature containing a relatively small number of targets may have high accuracy for predicting invasive ovarian cancer. Furthermore, we may be able to distinguish borderline tumors from early invasive ovarian cancers. We will continue to test the hypothesis that serum miRNA signatures may allow early detection of malignant ovarian carcinomas.

Publications

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  • Zheng XF, Acharya SS, Choe KN, Nikhil K, Adelmant G, Satapathy SR, Sharma S, Viccaro K, Rana S, Natarajan A, Sicinski P, Marto JA, Shah K, Chowdhury D. A mitotic CDK5-PP4 phospho-signaling cascade primes 53BP1 for DNA repair in G1. Nat Commun 2019; 10:4252. PubMed
  • Nikhil K, Chang L, Viccaro K, Jacobsen M, McGuire C, Satapathy SR, Tandiary M, Broman MM, Cresswell G, He YJ, Sandusky GE, Ratliff TL, Chowdhury D, Shah K. Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer. Cancer Lett 2019; 448:182-196. PubMed
  • Tomasik B, Chałubińska-Fendler J, Chowdhury D, Fendler W. Potential of serum microRNAs as biomarkers of radiation injury and tools for individualization of radiotherapy. Transl Res 2018; 201:71-83. PubMed
  • Botuyan MV, Cui G, Drané P, Oliveira C, Detappe A, Brault ME, Parnandi N, Chaubey S, Thompson JR, Bragantini B, Zhao D, Chapman JR, Chowdhury D, Mer G. Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein. Nat Struct Mol Biol 2018. PubMed
  • Meghani K, Fuchs W, Detappe A, Drané P, Gogola E, Rottenberg S, Jonkers J, Matulonis U, Swisher EM, Konstantinopoulos PA, Chowdhury D. Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas. Cell Rep 2018; 23:100-111. PubMed
  • Galanos P, Pappas G, Polyzos A, Kotsinas A, Svolaki I, Giakoumakis NN, Glytsou C, Pateras IS, Swain U, Souliotis VL, Georgakilas AG, Geacintov N, Scorrano L, Lukas C, Lukas J, Livneh Z, Lygerou Z, Chowdhury D, Sørensen CS, Bartek J, Gorgoulis VG. Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability. Genome Biol 2018; 19:37. PubMed
  • Tomasik B, Fendler W, Chowdhury D. Serum microRNAs - potent biomarkers for radiation biodosimetry. 2018; 9:14038-14039. PubMed
  • Iniguez AB, Stolte B, Wang EJ, Conway AS, Alexe G, Dharia NV, Kwiatkowski N, Zhang T, Abraham BJ, Mora J, Kalev P, Leggett A, Chowdhury D, Benes CH, Young RA, Gray NS, Stegmaier K. EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing Sarcoma. Cancer Cell 2018; 33:202-216.e6. PubMed
  • Komseli ES, Pateras IS, Krejsgaard T, Stawiski K, Rizou SV, Polyzos A, Roumelioti FM, Chiourea M, Mourkioti I, Paparouna E, Zampetidis CP, Gumeni S, Trougakos IP, Pefani DE, O'Neill E, Gagos S, Eliopoulos AG, Fendler W, Chowdhury D, Bartek J, Gorgoulis VG. A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence. BMC Genomics 2018; 19:37. PubMed
  • Elias KM, Fendler W, Stawiski K, Fiascone SJ, Vitonis AF, Berkowitz RS, Frendl G, Konstantinopoulos P, Crum CP, Kedzierska M, Cramer DW, Chowdhury D. Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer. Elife 2017. PubMed
  • Drané P, Chowdhury D. TIRR and 53BP1- partners in arms. Cell Cycle 2017. PubMed
  • Drané P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Münch C, Harper JW, Chaudhuri J, Soutoglou E, Mer G, Chowdhury D. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature 2017; 543:211-216. PubMed
  • Fendler W, Malachowska B, Meghani K, Konstantinopoulos PA, Guha C, Singh VK, Chowdhury D. Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates. Sci Transl Med 2017. PubMed
  • Howitt BE, Strickland KC, Sholl LM, Rodig S, Ritterhouse LL, Chowdhury D, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression. Oncoimmunology 2017; 6:e1277308. PubMed
  • Chen CC, Moskwa P, Zinn PO, Hirshman BR, Choi YE, Shukla SA, Fendler W, Lu J, Golub TR, Hjelmeland A, Chowdhury D. 334 A Functional Screen Identifies miRNAs that Induce Radioresistance in Glioblastomas. Neurosurgery 2016; 63 Suppl 1:197-8. PubMed
  • Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, Garber JE, Chowdhury D, Wu CJ, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. 2016. PubMed
  • Choi YE, Meghani K, Brault ME, Leclerc L, He YJ, Day TA, Elias KM, Drapkin R, Weinstock DM, Dao F, Shih KK, Matulonis U, Levine DA, Konstantinopoulos PA, Chowdhury D. Platinum and PARP Inhibitor Resistance Due to Overexpression of MicroRNA-622 in BRCA1-Mutant Ovarian Cancer. Cell Rep 2016; 14:429-39. PubMed
  • Dinh TK, Fendler W, Chałubińska-Fendler J, Acharya SS, O'Leary C, Deraska PV, D'Andrea AD, Chowdhury D, Kozono D. Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer. Radiat Oncol 2016; 11:61. PubMed
  • Zheng XF, Kalev P, Chowdhury D. Emerging role of protein phosphatases changes the landscape of phospho-signaling in DNA damage response. DNA Repair (Amst) 2015. PubMed
  • Acharya SS, Fendler W, Watson J, Hamilton A, Pan Y, Gaudiano E, Moskwa P, Bhanja P, Saha S, Guha C, Parmar K, Chowdhury D. Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury. Sci Transl Med 2015; 7:287ra69. PubMed
  • Moskwa P, Zinn PO, Choi YE, Shukla SA, Fendler W, Chen CC, Lu J, Golub TR, Hjelmeland A, Chowdhury D. A functional screen identifies miRs that induce radioresistance in glioblastomas. Mol Cancer Res 2014. PubMed
  • Murphy AK, Fitzgerald M, Ro T, Kim JH, Rabinowitsch AI, Chowdhury D, Schildkraut CL, Borowiec JA. Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery. J Cell Biol 2014; 206:493-507. PubMed
  • Tubbs AT, Dorsett Y, Chan E, Helmink B, Lee BS, Hung P, George R, Bredemeyer AL, Mittal A, Pappu RV, Chowdhury D, Mosammaparast N, Krangel MS, Sleckman BP. KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G₁-phase lymphocytes. Mol Cell Biol 2014. PubMed
  • Kushwaha D, Ramakrishnan V, Ng K, Steed T, Nguyen T, Futalan D, Akers JC, Sarkaria J, Jiang T, Chowdhury D, Carter BS, Chen CC. A genome-wide miRNA screen revealed miR-603 as a MGMT-regulating miRNA in glioblastomas. 2014; 5:4026-39. PubMed
  • Shaltiel IA, Aprelia M, Saurin AT, Chowdhury D, Kops GJ, Voest EE, Medema RH. Distinct phosphatases antagonize the p53 response in different phases of the cell cycle. Proc Natl Acad Sci U S A 2014. PubMed
  • Choi YE, Battelli C, Watson J, Liu J, Curtis J, Morse AN, Matulonis UA, Chowdhury D, Konstantinopoulos PA. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells. 2014; 5:2678-87. PubMed
  • Wang M, Kern AM, Hülskötter M, Greninger P, Singh A, Pan Y, Chowdhury D, Krause M, Baumann M, Benes CH, Efstathiou JA, Settleman J, Willers H. EGFR-mediated chromatin condensation protects KRAS-mutant cancer cells against ionizing radiation. Cancer Res 2014. PubMed
  • Lee DH, Acharya SS, Kwon M, Drane P, Guan Y, Adelmant G, Kalev P, Shah J, Pellman D, Marto JA, Chowdhury D. Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks. Mol Cell 2014. PubMed
  • Kolacinska A, Morawiec J, Fendler W, Malachowska B, Morawiec Z, Szemraj J, Pawlowska Z, Chowdhury D, Choi YE, Kubiak R, Pakula L, Zawlik I. Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report. Mol Biol Rep 2014. PubMed
  • Li XL, Hara T, Choi Y, Subramanian M, Francis P, Bilke S, Walker RL, Pineda M, Zhu Y, Yang Y, Luo J, Wakefield LM, Brabletz T, Park BH, Sharma S, Chowdhury D, Meltzer PS, Lal A. A p21-ZEB1 complex inhibits epithelial-mesenchymal transition through the microRNA 183-96-182 cluster. Mol Cell Biol 2014; 34:533-50. PubMed
  • Choi YE, Pan Y, Park E, Konstantinopoulos P, De S, D'Andrea A, Chowdhury D. MicroRNAs down-regulate homologous recombination in the G1 phase of cycling cells to maintain genomic stability. Elife 2014; 3:e02445. PubMed
  • Johnson N, Johnson SF, Yao W, Li YC, Choi YE, Bernhardy AJ, Wang Y, Capelletti M, Sarosiek KA, Moreau LA, Chowdhury D, Wickramanayake A, Harrell MI, Liu JF, D'Andrea AD, Miron A, Swisher EM, Shapiro GI. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Proc Natl Acad Sci U S A 2013; 110:17041-6. PubMed
  • Li YH, Wang X, Pan Y, Lee DH, Chowdhury D, Kimmelman AC. Inhibition of non-homologous end joining repair impairs pancreatic cancer growth and enhances radiation response. PLoS ONE 2012; 7:e39588. PubMed
  • Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D. miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell 2011; 41:210-20. PubMed
  • Lee DH, Pan Y, Kanner S, Sung P, Borowiec JA, Chowdhury D. A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol 2010; 17:365-72. PubMed
  • Wang B, Li S, Qi HH, Chowdhury D, Shi Y, Novina CD. Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol 2009; 16:1259-66. PubMed
  • Lal A, Navarro F, Maher CA, Maliszewski LE, Yan N, O'Day E, Chowdhury D, Dykxhoorn DM, Tsai P, Hofmann O, Becker KG, Gorospe M, Hide W, Lieberman J. miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. Mol Cell 2009; 35:610-25. PubMed
  • Zhu P, Martinvalet D, Chowdhury D, Zhang D, Schlesinger A, Lieberman J. The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5'-diphosphate-ribose) polymerase-1. Blood 2009; 114:1205-16. PubMed
  • Wang H,Zhao A,Chen L,Zhong X,Liao J,Gao M,Cai M,Lee DH,Li J,Chowdhury D,Yang YG,Pfeifer GP,Yen Y,Xu X. Human RIF1 encodes an anti-apoptotic factor required for DNA repair. Carcinogenesis 2009; 30:1314-9. PubMed
  • Lal A,Pan Y,Navarro F,Dykxhoorn DM,Moreau L,Meire E,Bentwich Z,Lieberman J,Chowdhury D. miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat Struct Mol Biol 2009; 16:492-8. PubMed
  • Wang B,Zhao A,Sun L,Zhong X,Zhong J,Wang H,Cai M,Li J,Xu Y,Liao J,Sang J,Chowdhury D,Pfeifer GP,Yen Y,Xu X. Protein phosphatase PP4 is overexpressed in human breast and lung tumors. Cell Res 2009; 18:974-7. PubMed
  • Wang B, Zhao A, Sun L, Zhong X, Zhong J, Wang H, Cai M, Li J, Xu Y, Liao J, Sang J, Chowdhury D, Pfeifer GP, Yen Y, Xu X. Protein phosphatase PP4 is overexpressed in human breast and lung tumors. Cell Res 2008. PubMed
  • Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, Dykxhoorn DM, Weinstock DM, Pfeifer GP, Lieberman J. A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol Cell 2008; 31:33-46. PubMed
  • Chowdhury D, Lieberman J. Death by a thousand cuts: granzyme pathways of programmed cell death. Annu Rev Immunol 2008; 26:389-420. PubMed
  • Dykxhoorn DM, Chowdhury D, Lieberman J. RNA interference and cancer: endogenous pathways and therapeutic approaches. Adv Exp Med Biol 2008; 615:299-329. PubMed
  • Martinvalet D, Thiery J, Chowdhury D. Granzymes and cell death. Methods Enzymol 2008; 442:213-30. PubMed
  • Chowdhury D, Beresford PJ, Zhu P, Zhang D, Sung JS, Demple B, Perrino FW, Lieberman J. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell 2006; 23:133-42. PubMed
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