Charles Giardina

Professor

Department of Molecular and Cell Biology

Education

  • Ph.D. SUNY Stony Brook
  • Postdoctoral research, Cornell University

Research Interests

The inter- and intra-cellular signaling events required for maintaining the structure and function of intestinal epithelium, with a focus on those events involved in regulating epithelial cell proliferation and death. Molecular mechanisms of transcription factor regulation by chemical and physical injury.

Publications

    1. Giardina C, Wu CW. The identification of two antagonistic activities in a Xenopus oocyte extract that can modulate the in vitro transcription of RNA polymerase III genes. J Biol Chem. 265: 9121-30, 1990
    2. Giardina C, Perez-Riba M, Lis JT. Promoter melting and TFIID complexes on Drosophila genes in vivo. Genes & Development. 6: 2190-200, 1992
    3. Giardina C, Lis JT. DNA melting on yeast RNA polymerase II promoters. Science. 261: 759-62, 1993
    4. Giardina C, Lis JT. Polymerase processivity and termination on Drosophila heat shock genes. J Biol Chem. 268: 23806-11, 1993
    5. Giardina C, Lis JT. Sodium salicylate and yeast heat shock gene transcription. J Biol Chem. 270: 10369-72, 1995
    6. O’Brien T, Wilkins RC, Giardina C, Lis JT. Distribution of GAGA protein on Drosophila genes in vivo. Genes & Dev. 9: 1098-110, 1995
    7. Giardina C, Lis JT. Dynamic protein-DNA architecture of a heat shock promoter. Mol Cell Biol. 15: 2737 1995
    8. Giardina C, Inan MS. Nonsteroidal anti-inflammatory drugs, short-chain fatty acids, and reactive oxygen metabolism in human colorectal cancer cells. Biochim Biophys Acta. 1401: 277-88, 1998
    9. Giardina C, Boulares H, Inan MS. NSAIDs and butyrate sensitize a human colorectal cancer cell line to TNF-alpha and Fas ligation: the role of reactive oxygen species. Biochim et Biophys Acta. 1448: 425-38, 1999
    10. Boulares HA, Giardina C, Navarro CL, Khairallah EA, Cohen SD. Modulation of serum growth factor signal transduction in Hepa 1-6 cells by acetaminophen: an inhibition of c-myc expression, NF-kB activation, and Raf-1 kinase activity. Toxicol Sci. 48: 264-74, 1999

(*Toxicol Sci paper of the year)

    1. Hubbard AK, Giardina C. Regulation of ICAM-1 expression in macrophages. Inflammation 24:115-25, 2000
    2. Inan MS, Tolmacheva V, Wang Q-S, Rosenberg DW, and Giardina C. The transcription factor NF-kB participates in the regulation of epithelial cell turnover in the colon. Am J Physiol. 279: G1282-G1291, 2000
    3. Inan MS, Place R, Tolmacheva V*, Wang Q-S, Hubbard AK, Rosenberg DW, and Giardina C. IkB-beta related proteins in normal and transformed colonic epithelial cells. Mol Carcinog. 29: 25-36, 2000
    4. Yin L, Hubbard AK, and Giardina C. NF-kB regulates transcription of the mouse telomerase catalytic subunit. J Biol Chem. 275: 36671-5, 2000
    5. Inan MS, Rasoulpour RJ, Yin L, Hubbard AK, Rosenberg DW, Giardina C. The luminal short-chain fatty acid butyrate modulates NF-kB activity in a human colonic epithelial cell line. Gastroenterology. 118: 724-34, 2000.

(*Commentary: Maintaining gut homeostasis: the butyrate-NF-kappaB connection, Hodin R, Gastroenterology 118: 798-801)

    1. Boulares AH, Giardina C, Inan MS, Khairallah EA, Cohen SD. Acetaminophen inhibits NF-kB activation by interfering with the oxidant signal in murine Hepa 1-6 cells. Toxicol Sci. 55: 370-5, 2000
    2. Crowthers KC, Kline V, Giardina C, Lynes MA. Augmented humoral immune function in metallothionein-null mice. Toxicol Appl Pharmacol. 166: 161-72, 2000
    3. Koulich E, Nguyen T, Johnson K, Giardina C, D’Mello SR. NF-kB is involved in the survival of cerebellar granule neurons: association of IkB-beta phosphorylation with cell survival. J Neurochem. 76: 1188-1198, 2001
    4. Place RF, Haspeslagh D*, Hubbard AK, Giardina C. Cytokine-induced stabilization of newly synthesized IkB-alpha. Biochem Biophys Res Commun 283:813-20, 2001
    5. Hubbard AK, Thibodeau M, and Giardina C. Cellular and molecular mechanisms regulating silica-induced adhesion molecule expression in mice. J Environ Pathol Toxicol Oncol, 20: 45-51, 2001.
    6. Guda K, Giardina C, Nambiar P, Cui H, Rosenberg DW. Aberrant transforming growth factor-beta signaling in azoxymethane-induced mouse colon tumors. Mol Carcinog, 31: 204-213, 2001.
    7. Yin L, Laevsky G and Giardina C. Butyrate suppression of colonocyte NF-kB activation and cellular proteasome activity. J Biol Chem, 276: 44641-6, 2001.
    8. Giardina C and Hubbard AK. Growing old with NF-kB. Cell Stress & Chaperones, 7: 207-212, 2002.
    9. Nambiar P, Giardina C, Guda K, Aizu W, Raja R and Rosenberg DW. Role of the alternating reading frame (p19)-p53 pathway in an in vivo murine colon tumor model. Cancer Res, 62: 3667-7, 2002.
    10. Dong, M, Guda, K, Nambiar, P, Belinsky, G, Giardina C, Rosenberg DW. Alterations in COX2 and cPLA2 expression in colon tumors suggest multiple mechanisms for tumor promotion. Carcinogenesis 24: 307-15, 2003.
    11. Place RF, Haspeslagh D, Giardina C. Cytokine-induced stabilization of newly synthesized IkB-alpha prevents sequential rounds of NF-kappaB activation. J Cell Physiol 195: 470-8, 2003.
    12. Brown JD, Strbuncelj M, Giardina C, O’Neill RJ. Interspecific hybridization induced amplification of Mdm2 on double minutes in a Mus hybrid. Cytogenetics & Genome Research 98: 184-8, 2002.
    13. Aizu W, Guda K, Nambiar P, Xin T, Rosenberg DW, Giardina C, p53 and its co-activator p300 can be inversely regulated in response to DNA damage. Toxicol Lett 144: 213-224, 2003.
    14. Thibodeau M, Giardina C, Andrea K. Hubbard. Silica induced caspase activation in mouse alveolar macrophages is dependent upon mitochondrial activity and aspartic proteases. Toxicological Sciences 76: 91-101, 2003.
    15. Thibodeau M, Giardina C, Helble J, Knecht D, Hubbard AK. Silica induced apoptosis in mouse alveolar macrophages is initiated by lysosomal activity. Toxicol Sci 80:34-48. 2004.
    16. Dong M, Guda K, Nambiar P, Nakanishi M, Giardina C, Lichtler, Rosenberg DW. Pref-1: a potential biomarker of colon cancer sensitivity that acts as a differentiation inhibitor. Carcinogenesis 25: 2239-2246, 2004
    17. Xin T, Yin L, Giardina C. Butyrate suppresses Cox-2 activation in colon cancer cells through HDAC inhibition. Biochem Biophys Res Comm 317: 463-71, 2004.
    18. Xin T, Yin L, Washington R, Rosenberg DW, Giardina C. The p50-p50 NF-kB complex as a cytokine-specific repressor of gene activation. Mol Cell Biochem 265: 171-183, 2004.
    19. Dong M, Johnson M, Rezaie A, Ilsley JNM, Nakanishi M, Sanders MM, Forouhar F, Levine J, Montrose DC, Giardina C, Rosenberg DW. Cytosolic Phospholipase A2 levels correlate with apoptosis in human colon tumorigenesis. Clin Cancer Res 11:2265-2271, 2005.
    20. Xin T, Yin L, Joshi S, Rosenberg DW and Giardina C. Regulation of Cox-2 expression at transcriptional elongation. J Biol Chem 280:15503-15509, 2005.
    21. Place RF, Noonan EJ, Giardina C. HDAC inhibitors suppress proteasome-mediated NF-kB activation in colon cancer cells. Biochemical Pharmacology 70:394-406, 2005.
    22. Place RF, Noonan EJ, Giardina C. HDACs and the senescent phenotype of cells. BMC Cell Biol. 6: 37, 2005.
      Hubbard AK, Mowbray S, Thibodeau M. and Giardina C. “Silica-induced Inflammatory Mediators and Pulmonary Fibrosis” in Fibrogenesis: Cellular and Molecular Events, Ed. M. Razzaque, Kluwer Academic/ Plenum Publishers, 2005.
    23. Aizu W, Belinsky GS, Flynn C, Noonan EJ, Boes CC, Godman CA, Doshi B, Nambiar PR, Rosenberg DW and Giardina C. Circumvention and reactivation of the p53 oncogene checkpoint in colon cancer cells. Biochem Pharmacol 72: 981-991, 2006.
    24. Noonan EJ, Place RF, Rasoulpour RJ, Giardina C, Hightower LE. Cell Number Dependent Regulation of Hsp70B’ expression: evidence of an extracellular regulator. J Cell Physiol 210: 201-211, 2007.
    25. Belinsky G, Giardina C, Rajan TV and Rosenberg DW. Expression of secretory phospholipase A2 in colon tumor cells potentiates tumor growth. Mol Carcinog 46:106-16, 2007.
    26. Stevens RG, Swede, H, Jablonski M, Parente M, Tirnauer JS, Heinen CD, Giardina C, Rajan TV, Rosenberg DW, Levine J. Aberrant Crypt Foci in Persons with a Family History of Colorectal Cancer. Cancer Lett 248:262-8, 2007.
    27. Ghanei M, Amiri S, Akbari H, Kosari F, Khalili AR, Alaeddini F, Aslani J, Giardina C, Haines DD. Correlation of sulfur mustard exposure and tobacco use with expression (immunoreactivity) of p53 protein in bronchial epithelium of Iranian “mustard lung” patients. Mil Med 172:70-4, 2007.
    28. Spurling CC, Godman CA, Noonan EJ, Rasmussen TP, Rosenberg DW, Giardina C. HDAC3 overexpression and colon cancer cell proliferation and differentiation. Molecular Carcinogenesis 47: 137 – 147, 2008.
    29. Noonan EJ, Place RF, Giardina C, Hightower LE. Hsp70B’ regulation and function. Cell Stress Chaperones12:219-229, 2007.
    30. Nakanishi M, Ménoret A, Belinsky GS, Giardina C, Godman CA, Vella AT, Rosenberg DW. Utilizing endoscopic technology to reveal real-time proteomic alterations in response to chemoprevention. Proteomics Clin Appl 1: 1660-1666, 2007
    31. Spurling CC, Suhl J, Boucher N, Nelson C, Rosenberg DW, Giardina C. The short chain fatty acid butyrate induces promoter demethylation and reactivation of RAR-beta2 in colon cancer cells. Nutr Cancer 60: 692-702, 2008.
    32. Noonan EJ, Giardina C, Hightower LE, Hsp70B’ and Hsp72 Form a Complex in Stressed Human Colon Cells and Each Contributes to Cytoprotection. Experimental Cell Research 314:2468-76, 2008.
    33. Godman C, Joshi R, Tierney BR, Greenspan E, Rasmussen TP, Rosenberg DW, and Giardina C, HDAC3 expression impacts multiple oncogenic signaling pathways in colon cancer cells. Cancer Biology & Therapy 7: 1571 – 1581, 2008.

(*Commentary: Dissecting HDAC3-mediated tumor progression, J M. Mariadason, Cancer Biology & Therapy 7: 1582-1584)

    1. Stevens R, Hurlstone R, Pretlow T, Giardina C, Rosenberg DW. Are aberrant crypt foci suitable surrogate endpoints for chemoprevention trials? Cancer Prev Res 1:215-6, 2008.
    2. Rosenberg DW, Giardina C, Tanaka T. Rodent models for the study of colon carcinogenesis. Carcinogenesis 30:183-96, 2008.
    3. Giardina C, Lis JT. Polymerase processivity and termination on Drosophila heat shock genes. J Biol Chem. 268: 23806-11, 1993
    4. Noonan E, Place R, Pookot D, Basak S, Whitson JM, Hirata H, Giardina C, and Dahiya R. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene 28:1714024, 2009.
    5. Hosseini-Khalili A, Haines DD, Modirian E, Soroush M, Khateri S, Joshi R, Zendehdel K, Ghanei M, Giardina C. Mustard gas exposure and carcinogenesis of the lung. Mutation Res 678:1-6, 2009.
    6. Verma R, Rigatti M, Belinsky G, Godman C, Giardina C. DNA damage response to the Mdm2 inhibitor Nutlin-3. Biochem Pharmacol 79:565-74, 2010.
    7. Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones 15: 431-42, 2010.
    8. Godman CA, Perdrizet G, Giardina C, Hightower LE. Hyperbaric Oxygen Treatment Induces Antioxidant Gene Expression. Annals NY Acad Sci 1197: 178-83, 2010.
    9. Ju J, Naura AS, Errami Y, Zerfaoui M, Kim H, Kim JG, Abd Elmageed ZY, Abdel-Mageed AB, Giardina C, Beg AA, Smulson ME, Boulares AH. Phosphorylation of p50 NF-kB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment. J Biol Chem 285: 41152-62, 2010.
    10. Cao L, Gibson JD, Miyamoto S, Sail V, Verma R, Rosenberg DW, Nelson CE, Giardina C. Intestinal lineage commitment of embryonic stem cells. Differentiation 81:1-10, 2011

(*Cover image)

  1. Montrose DC, Horelik NA, Madigan JP, Stoner GD, Wang LS, Bruno RS, Park HJ, Giardina C, Rosenberg DW Anti-inflammatory effects of lyophilized black raspberry powder in ulcerative colitis. Carcinogenesis 32: 343-50, 2011.
  2. Rigatti M, Verma R, Belinsky G, Rosenberg DW, Giardina C. Pharmacological inhibition of Mdm2 triggers growth arrest and promotes DNA breakage in mouse colon tumors and human colon cancer cells. Mol Carcinogenesis 51:363-78, 2012.
  3. Park HJ, Lee JY, Chung MY, Park YK, Bower AM, Koo SI, Giardina C, Bruno RS. Green tea extract suppresses NFkB activation and inflammatory responses in diet-induced obese rats with nonalcoholic steatohepatitis. J Nutr, 142:57-63, 2012.
  4. Giardina C, Madigan J, Godman Tierney C, Brenner B, Rosenberg DW. Vitamin D resistance and colon cancer prevention. Carcinogenesis, 33:475-82, 2012.
  5. Kuratnik A, Senapati VE, Verma R, Mellone BG, Vella AT, Giardina C. Acute sensitization of colon cancer cells to inflammatory cytokines by prophase arrest. Biochem Pharmacol 83:1217-28, 2012.
  6. Bo Dai, Giardina C, Rasmussen TP. Quantitation of Nucleosome Acetylation and other Histone Post-Translational Modifications Using Microscale NU-ELISA. Methods Mol Biol. 981:167-76, 2013.
  7. Fuller AM, Giardina C, Perdrizet G, Hightower LE, Godman CA. Hyperbaric oxygen preconditioning protects skin from UV-A damage. Cell Stress Chaperones 18: 97-107, 2013.
  8. Chopra AS, Kuratnik A, Scocchera EW, Wright DL, Giardina C. Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands. Cancer Biology & Therapy 14: 2013.
  9. Kuratnik A, Giardina C. Intestinal Organoids as Tissue Surrogates for Toxicological and Pharmacological Studies. Biochem Pharmacol 85:1721-6, 2013.
  10. Chopra A, Anderson A, Giardina C. Novel piperazine-based compounds inhibit microtubule dynamics and sensitize colon cancer cells to TNF-induced apoptosis. J Biol Chem 289:2978-91, 2014.
  11. Ononye S, Giardina C, Wright D, Anderson A. Studies on the antiproliferative effects of tropolone derivatives in Jurkat T-lymphocyte cells. Bioorganic & Medicinal Chemistry 22: 2188-93, 2014.
  12. Wright KT, Giardina C, Vella A. Therapeutic Targeting of the Inflammome, Biochem Pharmacol,15:184-91, 2014.
  13. Cao L, Kuratnik A, Xu W, Gibson JD, Kolling F, Falcone ER, Ammar M, Van Heyst MD, Wright DL, Nelson CE, Giardina C. Development of intestinal organoids as tissue surrogates: Cell composition and the Epigenetic control of differentiation. Mol Carcinog 54:189-202, 2015.
  14. Verma R, Chopra A, Giardina C, Sabbisetti V, Smyth JA, Hightower LE, Perdrizet GA. Hyperbaric oxygen therapy (HBOT) suppresses biomarkers of cell stress and kidney injury in diabetic mice. Cell Stress Chaperones 20:495-505, 2015.
  15. Giardina C, Nakanishi M, Khan A, Kuratnik A, Xu W, Brenner B, Rosenberg DW. Epigenetic regulation of VDR expression in Apc mutant mice, human colon cancer cells and adenomas. Cancer Prev Res 8: 387-99, 2015.

(*Cover image)

  1. Chopra A, Bond MJ, Bleiler M, Yeagley M, Wright D and Giardina C. Efficient activation of apoptotic signaling during mitotic arrest with AK301. PLOS ONE 11: e0153818, 2016Mo A, Jackson S, Varma K, Carpino A, Giardina C, Devers TJ, Rosenberg DW. Distinct transcriptional changes and epithelial-stromal interactions are altered in early stage colon cancer development. Mol Cancer Res. 2016
  2. Hanley MP, Kadaveru K, Perret C, Giardina C, Rosenberg DW Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development. Cancer Prev Res. 9: 812-820, 2016.
  3. Zhao Y, Hoang TH, Joshi P, Hong SH, Giardina C, Shin DG. A Route-Based Pathway Analysis Framework Integrating Mutation Information and Gene Expression Data. Methods S1046-2023(17)30039-7. 2017
  4. Harrison LE, Bleiler M, Giardina C. A look into centrosome abnormalities in colon cancer cells, how they arise and how they might be targeted therapeutically. Biochem Pharmacol. 2018 Jan;147:1-8. doi: 10.1016/j.bcp.2017.11.003.
  5. Bond MJ, Bleiler M, Harrison LE, Scocchera EW, Nakanishi M, G-Dayanan N, Keshipeddy S, Rosenberg DW, Wright DL, Giardina C. Spindle Assembly Disruption and Cancer Cell Apoptosis with a CLTC-Binding Compound. Mol Cancer Res. 2018 May 16. doi: 10.1158/1541-7786.MCR-18-0178.
  6. Harrison LE, Giardina C, Hightower LE, Anderson C, Perdrizet GA. Might hyperbaric oxygen therapy (HBOT) reduce renal injury in diabetic people with diabetes mellitus? From preclinical models to human metabolomics. Cell Stress Chaperones. 2018 Oct 30. doi: 10.1007/s12192-018-0944-8.
Dr. Charles Giardina
Contact Information
Emailcharles.giardina@uconn.edu
Phone860-486-0089
Fax860-486-4331
Mailing Address91 North Eagleville Road, Unit 3125, Storrs, CT 06269-3125
Office LocationBiology/Physics Building 322/323
CampusStorrs
Linkhttps://giardina.mcb.uconn.edu/