EPIGENETIC MEMORY OF INFLAMMATION

Falvo DJ, Grimont A, Zumbo P, Fall WB, Yang JL, Osterhoudt A, Pan G, Rendeiro AF, Meng Y, Wilkinson JE, Dündar F, Elemento O, Yantiss RK, Hissong E, Koche R, Betel D, Chandwani R. A reversible epigenetic memory of inflammatory injury controls lineage plasticity and tumor initiation in the mouse pancreas. Developmental Cell. 2023 Dec 18;58(24):2959-2973.e7. doi: 10.1016/j.devcel.2023.11.008. Epub 2023 Dec 5. PMID: 38056453.

A transient inflammatory injury storm has passed through Waddington’s landscape. Though the injury has resolved and the sun is shining, acinar cells trying to get back to homeostasis find that their epigenetic memory of inflammation pulls them towards cancer. Nothing was the same.

PANCREATIC CANCER INITIATION

Li AL, Sugiura K, Nishiwaki N, Suzuki K, Sadeghian D, Zhao J, Maitra A, Falvo D, Chandwani R, Pitarresi JR, Sims PA, Rustgi AK. FRA1 controls acinar cell plasticity during murine KrasG12D-induced pancreatic acinar to ductal metaplasia. Developmental Cell. 2024 Nov 18;59(22):3025-3042.e7. doi: 10.1016/j.devcel.2024.07.021. Epub 2024 Aug 22. PMID: 39178842; PMCID: PMC11576252.

Grimont A, Leach SD, Chandwani R. Uncertain Beginnings: Acinar and Ductal Cell Plasticity in the Development of Pancreatic Cancer. Cellular and Molecular Gastroenterology and Hepatology. 2022;13(2):369-382. doi: 10.1016/j.jcmgh.2021.07.014. Epub 2021 Aug 2. PMID: 34352406; PMCID: PMC8688164.

Alonso-Curbelo D, Ho YJ, Burdziak C, Maag JLV, Morris JP 4th, Chandwani R, Chen HA, Tsanov KM, Barriga FM, Luan W, Tasdemir N, Livshits G, Azizi E, Chun J, Wilkinson JE, Mazutis L, Leach SD, Koche R, Pe'er D, Lowe SW. A gene-environment-induced epigenetic program initiates tumorigenesis. Nature. 2021 Feb;590(7847):642-648. doi: 10.1038/s41586-020-03147-x. Epub 2021 Feb 3. PMID: 33536616; PMCID: PMC8482641.

Chandwani R, Allen PJ. Cystic Neoplasms of the Pancreas. Annual Reviews of Medicine. 2016;67:45-57. doi: 10.1146/annurev-med-051914-022011. Epub 2015 Nov 6. PMID: 26565675.

PANCREATIC CANCER MAINTENANCE

Duan X, Zhang T, Feng L, de Silva N, Greenspun B, Wang X, Moyer J, Martin ML, Chandwani R, Elemento O, Leach SD, Evans T, Chen S, Pan FC. A pancreatic cancer organoid platform identifies an inhibitor specific to mutant KRAS. Cell Stem Cell. 2024 Jan 4;31(1):71-88.e8. doi: 10.1016/j.stem.2023.11.011. Epub 2023 Dec 26. PMID: 38151022.

Dhara S, Chhangawala S, Chintalapudi H, Askan G, Aveson V, Massa AL, Zhang L, Torres D, Makohon-Moore AP, Lecomte N, Melchor JP, Bermeo J, Cardenas A 3rd, Sinha S, Glassman D, Nicolle R, Moffitt R, Yu KH, Leppanen S, Laderman S, Curry B, Gui J, Balachandran VP, Iacobuzio-Donahue C, Chandwani R, Leslie CS, Leach SD. Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility. Nature Communications. 2021 May 24;12(1):3044. doi: 10.1038/s41467-021-23237-2. PMID: 34031415; PMCID: PMC8144607.

Grbovic-Huezo O, Pitter KL, Lecomte N, Saglimbeni J, Askan G, Holm M, Melchor JP, Chandwani R, Joshi S, Haglund C, Iacobuzio-Donahue CA, Chiosis G, Tammela T, Leach SD. Unbiased in vivo preclinical evaluation of anticancer drugs identifies effective therapy for the treatment of pancreatic adenocarcinoma. Proceedings of the National Academy of Sciences. 2020 Dec 1;117(48):30670-30678. doi: 10.1073/pnas.1920240117. Epub 2020 Nov 16. PMID: 33199632; PMCID: PMC7720119.

Morris JP 4th, Yashinskie JJ, Koche R, Chandwani R, Tian S, Chen CC, Baslan T, Marinkovic ZS, Sánchez-Rivera FJ, Leach SD, Carmona-Fontaine C, Thompson CB, Finley LWS, Lowe SW. α-Ketoglutarate links p53 to cell fate during tumour suppression. Nature. 2019 Sep;573(7775):595-599. doi: 10.1038/s41586-019-1577-5. Epub 2019 Sep 18. PMID: 31534224; PMCID: PMC6830448.

EPIGENETIC Control of INFLAMMATION and Interferon RESPONSES

Chandwani R, Fang TC, Dewell S, Tarakhovsky A. Control of enhancer and promoter activation in the type I interferon response by the histone demethylase Kdm4d/JMJD2d. Frontiers in Immunology. 2023 May 16;14:1146699. doi: 10.3389/fimmu.2023.1146699. PMID: 37275914; PMCID: PMC10236313.

Nilsson-Payant BE, Uhl S, Grimont A, Doane AS, Cohen P, Patel RS, Higgins CA, Acklin JA, Bram Y, Chandar V, Blanco-Melo D, Panis M, Lim JK, Elemento O, Schwartz RE, Rosenberg BR, Chandwani R*, tenOever BR. The NF-κB Transcriptional Footprint Is Essential for SARS-CoV-2 Replication. Journal of Virology. 2021 Nov 9;95(23):e0125721. doi: 10.1128/JVI.01257-21. Epub 2021 Sep 15. PMID: 34523966; PMCID: PMC8577386. *co-corresponding author

Fang TC, Schaefer U, Mecklenbrauker I, Stienen A, Dewell S, Chen MS, Rioja I, Parravicini V, Prinjha RK, Chandwani R, MacDonald MR, Lee K, Rice CM, Tarakhovsky A. Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response. Journal of Experimental Medicine. 2012 Apr 9;209(4):661-9. doi: 10.1084/jem.20112343. Epub 2012 Mar 12. PMID: 22412156; PMCID: PMC3328357.

Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23. doi: 10.1038/nature09589. Epub 2010 Nov 10. PMID: 21068722; PMCID: PMC5415086.

KRAS and OTHER GENOMIC DETERMINANTS OF CANCER 

Gelfer R, Gulla A, Kalvin HL, Song Y, Harding J, Abou-Alfa GK, O'Reilly EM, Park W, Chandwani R, Wei A, Kingham P, Drebin J, Balachandran V, D'Angelica M, Soares K, Gonen M, Jarnagin WR. KRAS Variants Are Associated With Survival Outcomes and Genomic Alterations in Biliary Tract Cancers. JCO Precision Oncology. 2024 Dec;8:e2400263. doi: 10.1200/PO.24.00263. Epub 2024 Dec 6. PMID: 39642327.

McIntyre CA, Grimont A, Park J, Meng Y, Sisso WJ, Seier K, Jang GH, Walch H, Aveson VG, Falvo DJ, Fall WB, Chan CW, Wenger A, Ecker BL, Pulvirenti A, Gelfer R, Zafra MP, Schultz N, Park W, O'Reilly EM, Houlihan SL, Alonso A, Hissong E, Church GM, Mason CE, Siolas D, Notta F, Gonen M, Dow LE, Jarnagin WR, Chandwani R. Distinct clinical outcomes and biological features of specific KRAS mutants in human pancreatic cancer. Cancer Cell. 2024 Sep 9;42(9):1614-1629.e5. doi: 10.1016/j.ccell.2024.08.002. Epub 2024 Aug 29. PMID: 39214094; PMCID: PMC11419252.

Ecker BL, Shin P, Saadat LV, Court CM, Balachandran VP, Chandwani R, Drebin JA, Jarnagin WR, Kingham TP, Soares KC, Vakiani E, Wei AC, Kemeny NE, Smith JJ, Gonen M, D'Angelica MI. Genomic Stratification of Resectable Colorectal Liver Metastasis Patients and Implications for Adjuvant Therapy and Survival. Annals of Surgery. 2022 Feb 1;275(2):371-381. doi: 10.1097/SLA.0000000000005315. PMID: 34793355; PMCID: PMC8754193.

Chakraborty S, Ecker BL, Seier K, Aveson VG, Balachandran VP, Drebin JA, D'Angelica MI, Kingham TP, Sigel CS, Soares KC, Vakiani E, Wei AC, Chandwani R, Gonen M, Shen R, Jarnagin WR. Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care. Clinical Cancer Research. 2021 Nov 1;27(21):5891-5899. doi: 10.1158/1078-0432.CCR-21-1906. Epub 2021 Aug 25. PMID: 34433650; PMCID: PMC8563403.

Boerner T, Drill E, Pak LM, Nguyen B, Sigel CS, Doussot A, Shin P, Goldman DA, Gonen M, Allen PJ, Balachandran VP, Cercek A, Harding J, Solit DB, Schultz N, Kundra R, Walch H, D'Angelica MI, DeMatteo RP, Drebin J, Kemeny NE, Kingham TP, Simpson AL, Hechtman JF, Vakiani E, Lowery MA, Ijzermans JNM, Buettner S, Koerkamp BG, Doukas M, Chandwani R*, Jarnagin WR. Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma. Hepatology. 2021 Sep;74(3):1429-1444. doi: 10.1002/hep.31829. PMID: 33765338; PMCID: PMC8713028. *co-corresponding author

Other publications

Yu YD, Halazun KJ, Chandwani R, Samstein B. Minimally invasive tools are necessary for the modern practice of liver surgery. Journal of Minimal Access Surgery. 2024 Jul 1. doi: 10.4103/jmas.jmas_377_23. Epub ahead of print. PMID: 38958005.

Banito A, Li X, Laporte AN, Roe JS, Sanchez-Vega F, Huang CH, Dancsok AR, Hatzi K, Chen CC, Tschaharganeh DF, Chandwani R, Tasdemir N, Jones KB, Capecchi MR, Vakoc CR, Schultz N, Ladanyi M, Nielsen TO, Lowe SW. The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer Cell. 2018 Mar 12;33(3):527-541.e8. doi: 10.1016/j.ccell.2018.01.018. Epub 2018 Mar 1. Erratum in: Cancer Cell. 2018 Aug 13;34(2):346-348. PMID: 29502955; PMCID: PMC5881394.

Ruda VM, *Chandwani R, Sehgal A, Bogorad RL, Akinc A, Charisse K, Tarakhovsky A, Novobrantseva TI, Koteliansky V. The roles of individual mammalian argonautes in RNA interference in vivo. PLoS One. 2014 Jul 3;9(7):e101749. doi: 10.1371/journal.pone.0101749. PMID: 24992693; PMCID: PMC4081796. *equal contribution first author

Chandwani R, Jarnagin WR. Through & Through Duct-to-Mucosa Pancreaticojejunostomy. In M. Tewari (Ed.) How I Do It: Surgery for Pancreatic and Periampullary Cancer. (Springer: Singapore, 2017).

Chandwani R, D’Angelica MI. Intra-arterial chemotherapy for colorectal liver metastases. In E de Santibanes, M de Santibanes, V Ardiles, F Alvarez, VC Busnelli (Eds.) Extreme Hepatic Surgery and Other Strategies: Increasing Resectability in Colorectal Liver Metastases. (Springer: New York, NY, 2017).

Yang JS, Maurin T, Robine N, Rasmussen KD, Jeffrey KL, Chandwani R, Papapetrou EP, Sadelain M, O'Carroll D, Lai EC. Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. Proceedings of the National Academy of Sciences. 2010 Aug 24;107(34):15163-8. doi: 10.1073/pnas.1006432107. Epub 2010 Aug 10. PMID: 20699384; PMCID: PMC2930549.

Gumbs AA, Duffy AJ, Chandwani R, Bell RL. Jejunojejunal anastomotic obstruction following laparoscopic Roux-en-Y gastric bypass due to non-absorbable suture: a report of seven cases. Obesity Surgery. 2006 Jan;16(1):12-5. doi: 10.1381/096089206775222131. PMID: 16417750.

Chandwani R, Jordan KA, Shacklett BL, Papasavvas E, Montaner LJ, Rosenberg MG, Nixon DF, Sandberg JK. Limited magnitude and breadth in the HLA-A2-restricted CD8 T-Cell response to Nef in children with vertically acquired HIV-1 infection. Scandinavian Journal of Immunology. 2004 Jan;59(1):109-14. doi: 10.1111/j.0300-9475.2004.01365.x. PMID: 14723629.

Ortiz GM, Hu J, Goldwitz JA, Chandwani R, Larsson M, Bhardwaj N, Bonhoeffer S, Ramratnam B, Zhang L, Markowitz MM, Nixon DF. Residual viral replication during antiretroviral therapy boosts human immunodeficiency virus type 1-specific CD8+ T-cell responses in subjects treated early after infection. Journal of Virology. 2002 Jan;76(1):411-5. doi: 10.1128/jvi.76.1.411-415.2002. PMID: 11739706; PMCID: PMC135693.

Spiegel HM, Chandwani R, Sheehy ME, Dobroszycki J, Fennelly G, Wiznia A, Radding J, Rigaud M, Pollack H, Borkowsky W, Rosenberg M, Nixon DF. The impact of early initiation of highly active antiretroviral therapy on the human immunodeficiency virus type 1-specific CD8 T cell response in children. Journal of Infectious Diseases. 2000 Jul;182(1):88-95. doi: 10.1086/315639. Epub 2000 Jun 27. PMID: 10882585.