Cancer Initiative and Genome Integrity

For more about Dr. Chakrabarti’s lab, visit his research lab webpage.

Research projects

1. Structure and function of RNA and ribonucleoprotein complexes.
2. Telomerase regulation and genome integrity in unicellular pathogens.
3. Post-transcriptional mRNA processing in cell proliferation and cancer. 

Representative Publications

1. Dey A, Chakrabarti K. Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites. Int J Mol Sci. 2018;19(2). Epub 2018/01/25. doi: 10.3390/ijms19020333. PMID: 29364142; 
2. Ares M, Jr., Chakrabarti K*. Stuttering against marginotomy. Nat Struct Mol Biol. 2008;15(1):18-9. Epub 2008/01/08. doi: 10.1038/nsmb0108-18. PMID: 18176550.
3. Sandhu R, Sanford S, Basu S, Park M, Pandya UM, Li B, Chakrabarti K*. A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei. Cell Res. 2013;23(4):537-51. Epub 2013/03/13. doi: 10.1038/cr.2013.35. PubMed PMID: 23478302; PMCID: PMC3616428.

For more about Dr. Dasgupta’s lab, visit https://biology.charlotte.edu/people/dasgupta/

Research Projects

1. Novel Targets in Cancer associated cachexia
2. Dual Targets in Pancreatic Tumor and Cachectic Muscle
3. Tumor-Host crosstalk

Representative Publications

1. Dasgupta A, Schmitt RE, Kono T, Lee C,Zoberi MI, Epstein SA, Schneider JZ, Hernandez A, Grandgenett PM, Caffrey TC, DiMaio DJ, Hollingsworth MA, and Doles JD. Journal of
   Experimental Medicine 2025 (in Press). Histidine decarboxylase inhibition attenuates
   cancer-associated muscle wasting. *Joint co-corresponding authors.
2. Dasgupta A* ¥ , Gibbard DF*, Schmitt RE, Arneson-Wissink PC, Ducharme AM, Bruinsma
   ES, Hawse JR, Jatoi A, Doles JD ¥ . PNAS 2023 Aug 22;120(34). A TGF-β/KLF10 signaling
   axis regulates atrophy-associated genes to induce muscle wasting in pancreatic cancer.
   *Joint co-first authors, ¥ Joint co-corresponding authors.
3. Dasgupta A, Arneson-Wissink PC, Schmitt RE, Cho DS, Ducharme AM, Hogenson TL,
   Krueger EW, Bamlet WR, Zhang L, Razidlo G, Fernandez-Zapico ME, Doles JD. JCI Insight.
   2022;7(2):e153842. Anti-cachectic regulator analysis reveals Perp-dependent anti-
   tumorigenic properties of 3-methyladenine in pancreatic cancer.
4. Dasgupta A, Shukla SK, Vernucci E, RJ, Abrego J, Mulder SE,Mullen N, Graves G,
   Buettner K, Thakur R, Murthy D, Attri KS, Chaika NV, Pacheco CG, Rai I, Engle DD,
   Grandgenett PM, Punsoni M, Reames BN, Teoh-Fitzgerald M, Oberley-Deegan R, Yu F,
   Klute KA, Hollingsworth MA, Zimmerman MC, Kamiya Mehla K, Sadoshima J, Tuveson D,
   and Singh PK. Journal of Experimental Medicine. J Exp Med (2020) 217 (7). SIRT1-NOX4
   Axis Regulates Muscle Atrophy in Cancer
5. Neyroud D, Laitano O, Dasgupta, A, Lopez C, Schmitt RE, Schneider JZ, Hammers DW,
   Sweeney HL, Walter GA, Doles J, Judge SM, & Judge AR. (2023). Communications biology,
   6(1), 519. Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1
   impedes pancreatic tumor growth.

For more about Dr. Dreau’s lab, visit his research lab webpage

Research projects

1. Chemokine heterodimerization and signaling
2. Chemokine signaling and immunotherapy
3. Inflammation and cancer progression
4. 3D modeling of tumor and bone metastasis

Representative Publications

1. Nguyen KTP, Volkman B, Dréau D, Nesmelova IV, 2022. A new obligate CXCL4-CXCL12
   heterodimer for studying chemokine heterodimer activities and mechanisms. Sci Rep.
   12(1):17204. doi: 10.1038/s41598-022-21651-0. PMID:36229490
2. Nguyen KTP, Druhan LJ, Avalos BR, Zhai L, Rauova L, Nesmelova IV, Dréau D, 2020.
   CXCL12-CXCL4 heterodimerization prevents CXCL12-driven breast cancer cell migration.
   Cell Signal. 66:109488. doi: 10.1016/j.cellsig.2019.109488. PMID:31785332
3. Rego SL, Helms RS, Dréau D, 2014. Breast tumor cell TACE-shed MCSF promotes pro-
   angiogenic macrophages through NF-κB signaling. Angiogenesis. 17(3):573-85. doi:
   10.1007/s10456-013-9405-2. PMID:24197832
4. Lance A, Yang CC, Swamydas M, Dean D, Deitch S, Burg KJ, Dréau D, 2016. Increased
   extracellular matrix density decreases MCF10A breast cell acinus formation in 3D culture
   conditions. J Tissue Eng Regen Med. 10(1):71-80. doi: 10.1002/term.1675. PMID:23404906
5. Bland E, Dréau D, Burg KJ, 2013. Overcoming hypoxia to improve tissue-engineering
   approaches to regenerative medicine. J Tissue Eng Regen Med. 7(7):505-14. doi:
   10.1002/term.540. PMID:22761177

For more about Dr. Mukherjee’s lab: https://biology.charlotte.edu/directory/pinku-mukherjee-phd/
and https://oncotab.com/about/

Research / Translational projects

1. Immunotherapy of Epithelial Ductal Cancers (current focus: triple negative metastatic breast cancers and pancreatic ductal adenocarcinomas)
   • Antibody engineering-Bispecific antibody/Bispecific T cell engagers
   • CAR T cells and CAR NK cell therapies
   • Theranoustics and ADCs (including nanoparticle loaded therapeutics)
2. Immuno-Oncology related to tumor associated antigen, MUC1
   • Metabolomics
   • Oncogenic signaling
3. Tumor cell Intrinsic Treatment Resistance Mechanisms

Representative Publications/Patents

1. US9845362B2, Compositions comprising chimeric antigen receptors, T cells comprising the same, and methods of using the same
2. US9090698B2, Tumor specific antibodies and uses therefor
3. US20180043038A1, Tumor specific antibody conjugates and uses therefor
4. Dahlia M. Besmer, Jennifer Curry, Lopamudra Das Roy, , et al and Pinku Mukherjee (2011). Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 have a profound defect in tumor growth and metastasis. Cancer Research: 71:4432-4442. PMID: 21558393
5. Sritama Nath and Pinku Mukherjee (2014) MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends in Molecular Medicine. 2014 Jun;20(6):332-42. PMID: 24667139
6. Ru Zhou, Lopamudra Das Roy, Mahboubeh Yazdanifar, Chad Livasy and Pinku Mukherjee (2017). The use of tMUC1 highly specific chimeric antigen receptor-redirected T cells for the eradication of triple negative breast cancer, J Immunol May 1, 2017, 198 (1sup.) 198.10. PMID: 31178870
7. Vanessa J Kelly, Shu-Ta Wu, et al, Pinku Mukherjee (2020). Preclinical evaluation of an 111In/225Ac theranostic targeting transformed MUC1 for triple negative breast cancer. Theranostics 2020; 10(15): 6946- 6958; doi:10.7150/thno.38236 PMID: 32550914
8. Tarannum, Mubin; Hossain, Md; Holmes, Bryce; Yan, Shan; Mukherjee, Pinku; Vivero-Escoto, Juan. (2021). Advanced Nanoengineering Approach for Target-Specific, Spatiotemporal, and Ratiometric Delivery of Gemcitabine-Cisplatin Combination for Improved Therapeutic Outcome in Pancreatic Cancer. Small 2022 Jan;18(2):e2104449. PMID: 34758094

For more about Dr. Richardson’s lab, visit her research lab webpage.

Research projects

1. DNA damage and translocations caused by bioflavonoids.
2. DNA repair pathway choice.
3. In vivo models of homologous recombination and non-homologous endjoining to repair double strand breaks. 

Representative Publications

1. Goodenow D, Emmanuel F, Berman C, Sahyouni M, Richardson C. Bioflavonoids cause DNA double-strand breaks and chromosomal translocations through topoisomerase II-dependent and -independent mechanisms. Mut Res: Gen Tox Env Gen. available online 2020.
2. Bariar BB, Vestal CV, Deem B, Goodenow D, Ughetta M, Engledove W, Sahyouni M, Richardson C. Bioflavonoids promote stable translocations between MLL–AF9 breakpoint cluster regions independent of chromosomal context: model system to screen environmental risks. Env. Mol. Mutagenesis, 2019 PMID: 30387535. 
3. White, R, Sung, P, Vestal, CG, Benedetto, G., Cornelio, N., and Richardson, C. Double-strand break repair by interchromosomal recombination: an in vivo repair mechanism utilized by multiple somatic tissues in mammals.  PlosONE, 8(12): 1-16, 2013. e84379. PMID: 24349572 PMCID: PMC3862804

For more about Dr. Ren’s lab, visit his lab webpage

Research projects

1. Exploring the Roles of Liquid-Liquid Phase Separation in Gene Regulation
2. Single-Molecule Imaging of Epigenetic Processes
3. Epigenetic Mechanisms in Cancers
4. Therapeutic Targeting of Epigenetic Modifications and LLPS

Representative Publications

1. Steven Ingersoll, Xiaojun Ren # (2025) Hypoxia-specific transcriptional condensates drive
   metastasis. Trends Cell Biol. 2025 Jun;35(6):456-458. Pubmed/40379526
2. Kyle Brown, Pin Yu Chew, Steven Ingersoll, Jorge R Espinosa, Anne Aguirre, Axel
   Espinoza, Joey Wen, Kalkidan Astatike, Tatiana G Kutateladze, Rosana Collepardo-
   Guevara, Xiaojun Ren # (2023) Principles of assembly and regulation of condensates of
   Polycomb repressive complex 1 through phase separation. Cell Reports. 2023 Oct
   31;42(10):113136. Pubmed/37756159
3. Samantha Kent, Kyle Brown, Chou-Hsun Yang, Njood Alsaihati, Christina Tian, Haobin
   Wang, Xiaojun Ren # (2020) Phase-Separated Transcriptional Condensates Accelerate
   Target-Search Process Revealed by Live-Cell Single-Molecule Imaging. Cell Reports, 2020
   Oct 13;33(2):108248. Pubmed/33053359
4. Roubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao
   Ngoc Huynh, Chao Yu Zhen, Brian Ma, Haobin Wang, Xiaojun Ren # (2019) Nuclear
   condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase
   separation. J Biol Chem. 2019 Feb 1;294(5):1451-1463. Pubmed/30514760
5. Roubina Tatavosian, Huy Nguyen Duc, Thao Ngoc Huynh, Dong Fang, Benjamin Schmitt,
   Xiaodong Shi, Yiming Deng, Christopher Phiel, Tingting Yao, Zhiguo Zhang, Haobin Wang,
   Xiaojun Ren # (2018) Live-cell single-molecule dynamics of PcG proteins imposed by the
   DIPG H3. 3K27M mutation. Nat Commun. 2018 May 25;9(1):2080. Pubme/29802243

For more about Dr. Tomida’s lab, visit his research lab webpage.

Research projects

1. Define factors leading to chemoresistance in prostate cancer (knockout mouse and cell
   models).
2. Determine REV7 functions, which are critical for integrating multiple processes that
   determine viability and genome stability.
3. Identify new roles for REV7 in the regulation of p53’s activities in cell cycle control,
   apoptosis, DNA repair, and other cellular processes.
4. Characterize the protein complex of DNA repair proteins.

Representative Publications

1. Tomida J*, Takata KI, Bhetawal S, Person MD, Chao HP, Tang DG, Wood RD. FAM35A
   associates with REV7 and modulates DNA damage responses of normal and BRCA1-
   defective cells. EMBO J. 2018;37(12). Epub 2018/05/24. DOI:
   https://doi.org/10.15252/embj.201899543. PMID: 29789392. co-corresponding author
2. Fackrell K, Bobins L, Parul, and Tomida J*. FAM35A/SHLD2/RINN2: A novel
   determinant of DSB repair pathway choice and genome stability in cancer. Environ Mol
   Mutagen 61(7):709-715, 8/2020. e-Pub 7/2020. DOI: https://doi.org/10.1002/em.22379.
   PMID: 32306447
3. Biller M, Kabir S, Nipper S, Allen S, Kayali Y, Kuncik S, Sasanuma H, Wood R, Pei Zhou,
   Vaziri C, Tomida J*. REV7 associates with ATRIP and inhibits ATR kinase activity.
   bioRxiv. DOI: https://doi.org/10.1101/2025.01.17.633588. PMID: 39868202
4. Biller M, Kabir S, Boado C, Nipper S, Saffa A, Tal A, Allen S, Sasanuma H, Dréau D,
   Vaziri C, Tomida J*. REV7-p53 interaction inhibits ATM-mediated DNA damage
   signaling. Cell Cycle 1-14, 4/2024. DOI:https://doi.org/10.1080/15384101.2024.2333227.
   PMID: 38557443
5. Tomida J, Takata K, Lange SS, Schibler AC, Yousefzadeh MJ, Bhetawal S, Dent SY,
   Wood RD. REV7 is essential for DNA damage tolerance via two REV3L binding sites in
   mammalian DNA polymerase ζ. Nucleic Acids Res 43(2):1000-11, 1/2015. e-Pub
   1/2015. DOI: https://doi.org/10.1093/nar/gku1385. PMCID: PMC4333420

For more about Dr. Truman’s lab, visit his research lab webpage.

Research projects

1. Understanding the impact of Hsp70 post-translational modifications on the DNA damage
   response
2. Characterizing the structure of the Ribonucleotide reductase (RNR)-chaperone megacomplex
   using Cryo-EM and XL-MS
3. Identifying novel anticancer therapies that disrupt RNR-chaperone interactions

Representative Publications

1. Omkar S†, Mitchem MM†, Hoskins JR, Shrader C†, Kline JT, Nitika†, Fornelli L, Wickner S,
   Truman A.W.* (2024). Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes
   proteostasis and translational fidelity. PLOS Genetics. 2024;20(12):e1011338. doi:
   10.1371/journal.pgen.1011338.
2. Omkar, S†., A. Rysbayeva‡, and Truman A.W.* (2023). Understanding chaperone
   specificity: evidence for a ‘client code’. Trends Biochem Sci, 2023. 48(8): p. 662-664.
3. Nitika†, Zheng B, Ruan L, Kline JT, Omkar, S. †, Sikora J, Torres MT, Wang Y, Takakuwa
   JE‡, Huguet R, Klemm C, Segarra VA, Winters MJ, Pryciak PM, Thorpe PH, Tatebayashi K,
   Li R, Fornelli L and Truman A.W.* (2022). Comprehensive characterization of the Hsp70
   interactome reveals novel client proteins and interactions mediated by post-translational
   modifications. PLoS Biol 20(10): p. e3001839.
4. Knighton, L.E. †, Nitika†, Omkar, S. †, and Truman, A.W.* (2022). The C-terminal domain of
   Hsp70 is responsible for paralog-specific regulation of ribonucleotide reductase. PLoS Genet
   18, e1010079
5. Nitika†, Blackman, J.S. ‡, Knighton, L.E. †, Takakuwa, L.E. ‡, Stuart K. Calderwood and
   Truman A. W.* (2020) Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1
   as a hub for anticancer drug resistance. Sci Rep 10, 13831. https://doi.org/10.1038/s41598-
   020-70764-x.

For more about Dr. van Oosten-Hawle’s lab, visit her research lab webpage: https://www.vanoostenhawlelab.com/

Research projects

1.     Transcellular chaperone signaling in the regulation of organismal health and disease

2.     Gut-to-neuron stress signaling promoting neuroprotective and behavioral responses

3.     Organismal proteostasis pathways in the regulation of the pathogen and DNA damage response

Representative Publications

1.     Good SC, Dewison KM, Radford SE, van Oosten-Hawle P. Global Proteotoxicity Caused by Human β₂ Microglobulin Variants Impairs the Unfolded Protein Response in C. elegans. International Journal of Molecular Sciences. 2021; 22(19):10752.

2.      O’Brien, D., Jones, L., Good, S., Miles, J., Aston, R., Smith, C., Vijayabaskar, S., Westhead, D., and van Oosten-Hawle, P. (2018) A PQM-1-mediated response mediates transcellular chaperone signaling and organismal proteostasis. Cell Reports. 2018 Jun 26;23(13):3905-3919

3.     Miles, J., van Oosten-Hawle P. Tissue-specific RNAi tools to identify components for systemic stress signaling. Journal of Visual Experiments (JOVE) (2020) May 16;(159).

4.     van Oosten-Hawle, P., Porter, R.S., and Morimoto, R. I. (2013). Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153, 1366-1378.

For more about Dr. Yan’s lab, visit his research lab webpage

Research projects

1. To decipher the regulation and crosstalk of SSB/DSB repair and signaling pathways
2. To elucidate the molecular mechanisms of nucleolar and mitochondrial DNA/RNA stability
3. To dissect the molecular details of biomolecular condensates (liquid-liquid phase separation)
   in genome integrity
4. To modulate the mechanisms of APE1, and APE2, and PARP1 in genome integrity for the
   treatment of BRCA1-/BRCA2-related cancers

Representative Publications

1. Zhao H, Li J, You Z, Lindsay HD, Yan S*. 2024. Distinct regulation of ATM signaling by DNA
   single-strand breaks and APE1. Nature Communications. 15 (1): 6517. (PMCID:
   PMC11306256; PMID: 39112456) DOI: https://doi.org/10.1038/s41467-024-50836-6
2. Li J, Zhao H, McMahon A, Yan S*. 2022. APE1 assembles biomolecular condensates to
   promote the ATR-Chk1 DNA damage response in nucleolus. Nucleic Acids Research.
   50(18):10503-10525.  (PMCID: PMC9561277; PMID: 36200829). DOI:
   https://doi.org/10.1093/nar/gkac853
3. Lin Y, Raj J, Li J, Ha A, Hossain MA, Richardson C, Mukherjee P, Yan S*. 2020. APE1
   senses DNA single-strand breaks for repair and signaling. Nucleic Acids Research.
   48(4):1925-1940. (PMCID: PMC7038996; PMID: 31828326) DOI:
   https://doi.org/10.1093/nar/gkz1175
4. Lin Y, Bai L, Cupello S, Hossain MA, Deem B, McLeod M, Raj J, Yan S*. 2018. APE2
   promotes DNA damage response pathway from a single-strand break. Nucleic Acids
   Research. 46 (5): 2479-2494. (PMCID: PMC5861430; PMID: 29361157) DOI:
   https://doi.org/10.1093/nar/gky020
5. Willis J, Patel Y, Lentz B ,  Yan S * . 2013. APE2 is required for ATR-Chk1 checkpoint
   activation in response to oxidative stress. Proceedings of the National Academy of Sciences
   of the United States of America. 110 (26): 10592-10597. (PMCID: PMC3696815; PMID:
   23754435).  DOI: http://dx.doi.org/10.1073/pnas.1301445110