Thomas J. Knobloch, MS, PhD

Senior Scientist
Adjunct Faculty
OSU Comprehensive Cancer Center
Molecular Carcinogenesis and Chemoprevention Program
Food Innovaton Center

California 5-Peak Challenge

Contact

1841 Neil Avenue
434 Cunz Hall
Columbus, OH, 43210
Email: knobloch.1@osu.edu
Phone: 614-292-4168
Website: The Ohio State University – Comprehensive Cancer Center – Molecular Carcinogenesis and Cancer Chemoprevention Program

Professional Overview

I was originally trained in graduate school as a natural scientist using phylogenetics and taxonomic-systematics as tools for defining (re-defining) species relationships in North American Cyprinidae (that's minnows to most of the world). These studies transitioned into taxonomic characterization of Bacillariophyta (diatoms) in fresh water system in Northern Ohio, especially those consumed by algivorous minnows. Eventually this path lead to work with Ohio Department of Natural Resources (ODNR) investigating the invasive species Petromyzon marinus, the sea lamprey, and the control measures in the Great Lakes' tributaries.

I moved from Cleveland to Columbus, OH just as the original Arthur G. James Cancer Hospital and Research Institute was being finished, and hiring for qualified researchers was at a premium. I was uniquely unqualified for a career in molecular carcinogenesis, but was hired and mentored by a young physician scientist (Mark A. Dayton, PhD, MD) in the Division of Hematology & Oncology within the College of Medicine & Public Health.

I returned to graduate school and joined the research group of Jas Campbell Lang, PhD in the Department of Otolaryngology investigating a novel gene of then unknown function, designated by us as GRS (Glasgow Rearranged Sequence). Later our gene and its variants reported by others under different names was reconciled by annotation as BCL2A1, a cell death regulator. For the next 6 years I would immerse myself in head and neck cancer etiology, biology, molecular profiles, treatment options, and prevention strategies.

Subsequently, I joined the new School of Public Health with Christopher M. Weghorst, PhD to continue work in head and neck cancers, with empahsis on oral cancers and the possile role of natural products, such as black raspberries, as dietary intervention tools. This emerging science of black raspberry-mediated cancer chemoprevention was spearheaded by fundatmental studies by Gary D. Stoner, PhD, and would eventually shape the next 20 years of my research efforts.

Gaining experience as a Fellow via an NCI T32 Training Grant in Molecular Carcinogenesis, I continued on within the Division of Environmental Health Sciences in the new independent College of Public Health. Using both preclinical models of experimental oral carcinogenesis and early phase human clinical trials, I invesigated the striking ability of black raspberry phytochemicals to reduce bomarkers of DNA damage, chronic non-resolving inflammation, and oxidateive stress. All of these are classic hallmark features of cancer.

Most recently I have embarked on two newly emerging fields of intense concern. 

First, a topic of emphasis by the CDC and EPA is the role harmful algal blooms (HABs) on human health. My interest in this area is determining if dietary black raspberry interventions can reduce tumor incidence and multiplicity (burden) during cyanotoxin-mediated liver cancer promotion.

Second, a national health crisis exsists for firefighters, who have career-long exposures to numerous combustion-associated carcinogens and occupational stressors. The leading cause of deaths in firefighters is in flux between cardiac/cardiovascular events and occupation-associated cancers, including lung cancer. Nutritional interventions leveraging specific functional food components can be used to mediate these stressors (proinflammatory cytokines, oxidative damage, non-resolving inflammation) in this high at-risk population. Or at least that's the idea.

Education

B.S. (Biology/Interdisciplinary Program in Neuroscience), John Carroll University
M.S. (Ichthyology and Diatom Phylogenetics), John Carroll University
Ph.D. (Molecular, Cellular and Developmental Biology), The Ohio State University
T32 NCI Training Fellowship (Molecular Carcinogenesis), The Ohio State University

Selected Publications

2019 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Knobloch TJ, Peng J, Hade EM, Cohn DE, Ruffin MT 4th, Schiano MA, Calhoun BC, McBee WC Jr, Lesnock JL, Gallion HH, Pollock J, Lu B, Oghumu S, Zhang Z, Sears MT, Ogbemudia BE, Perrault JT, Weghorst LC, Strawser E, DeGraffinreid CR, Paskett ED, Weghorst CM. Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.
Cancer Causes Control. 2019 Oct;30(10):1087-1100. doi: 10.1007/s10552-019-01221-y. Epub 2019 Aug 21.
PMID: 31435875

Knobloch TJ, Ryan NM, Bruschweiler-Li L, Wang C, Bernier MC, Somogyi A, Yan PS, Cooperstone JL, Mo X, Brüschweiler RP, Weghorst CM, Oghumu S.
Metabolites. 2019 Jul 11;9(7). pii: E140. doi: 10.3390/metabo9070140. Metabolic Regulation of Glycolysis and AMP Activated Protein Kinase Pathways during Black Raspberry-Mediated Oral Cancer Chemoprevention.
PMID: 31336728 Free PMC Article

Tu P, Xue J, Bian X, Chi L, Gao B, Leng J, Ru H, Knobloch TJ, Weghorst CM, Lu K. Dietary administration of black raspberries modulates arsenic biotransformation and reduces urinary 8-oxo-2'-deoxyguanosine in mice. Toxicol Appl Pharmacol. 2019 Aug 15;377:114633. doi: 10.1016/j.taap.2019.114633. Epub 2019 Jun 20.
PMID: 31229487

2018 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Mrdjen I, Morse MA, Ruch RJ, Knobloch TJ, Choudhary S, Weghorst CM, Lee J. Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice. Toxins (Basel). 2018 Oct 28;10(11). pii: E435. doi: 10.3390/toxins10110435.
PMID: 30373283 Free PMC Article

Tu P, Bian X, Chi L, Gao B, Ru H, Knobloch TJ, Weghorst CM, Lu K. Characterization of the Functional Changes in Mouse Gut Microbiome Associated with Increased Akkermansia muciniphila Population Modulated by Dietary Black Raspberries. ACS Omega. 2018 Sep 30;3(9):10927-10937. doi: 10.1021/acsomega.8b00064. Epub 2018 Sep 10.
PMID: 30288460 Free PMC Article

Teegarden MD, Knobloch TJ, Weghorst CM, Cooperstone JL, Peterson DG. Storage conditions modulate the metabolomic profile of a black raspberry nectar with minimal impact on bioactivity. Food Funct. 2018 Sep 19;9(9):4593-4601. doi: 10.1039/c8fo00639c.
PMID: 30022172 Free PMC Article

2017 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Oghumu S, Casto BC, Ahn-Jarvis J, Weghorst LC, Maloney J, Geuy P, Horvath KZ, Bollinger CE, Warner BM, Summersgill KF, Weghorst CM, Knobloch TJ. Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries. Front Immunol. 2017 Oct 23;8:1325. PMID: 29109723

Poi MJ, Knobloch TJ, Li J. Deletion of RDINK4/ARF enhancer: A novel mutation to "inactivate" the INK4-ARF locus. DNA Repair (Amst). 2017 Sep;57:50-55. Review. PMID: 28688373

2016 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Oghumu S, Knobloch TJ, Terrazas C, Varikuti S, Ahn-Jarvis J, Bollinger CE, Iwenofu H, Weghorst CM, Satoskar AR. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators. Int J Cancer. 2016 Sep 15;139(6):1379-90. PMID: 27164411

Knobloch TJ, Uhrig LK, Pearl DK, Casto BC, Warner BM, Clinton SK, Sardo-Molmenti CL, Ferguson JM, Daly BT, Riedl K, Schwartz SJ, Vodovotz Y, Buchta AJ Sr, Schuller DE, Ozer E, Agrawal A, Weghorst CM. Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry Phytochemical-Rich Troche. Cancer Prev Res (Phila). 2016 Feb;9(2):159-71. PMID: 26701664

2015 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Poi MJ, Knobloch TJ, Sears MT, Warner BM, Uhrig LK, Weghorst CM, Li J. Alterations in RD(INK4/ARF) -mediated en bloc regulation of the INK4-ARF locus in human squamous cell carcinoma of the head and neck. Mol Carcinog. 2015 Jul;54(7):532-42. PMID: 24302590

2014 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Warner BM, Casto BC, Knobloch TJ, Accurso BT, Weghorst CM. Chemoprevention of oral cancer by topical application of black raspberries on high at-risk mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014 Dec;118(6):674-83. PMID: 25457886

Joehlin-Price AS, Elkins CT, Stephens JA, Cohn DE, Knobloch TJ, Weghorst CM, Suarez AA. Comprehensive evaluation of caspase-14 in vulvar neoplasia: an opportunity for treatment with black raspberry extract. Gynecol Oncol. 2014 Dec;135(3):503-9. PMID: 25256208

Poi MJ, Knobloch TJ, Sears MT, Uhrig LK, Warner BM, Weghorst CM, Li J. Coordinated expression of cyclin-dependent kinase-4 and its regulators in human oral tumors. Anticancer Res. 2014 Jul;34(7):3285-92. PMID: 24982332

Mace TA, King SA, Ameen Z, Elnaggar O, Young G, Riedl KM, Schwartz SJ, Clinton SK, Knobloch TJ, Weghorst CM, Lesinski GB. Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling. Cancer Immunol Immunother. 2014 Sep;63(9):889-900. PMID: 24893859

2013 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Guo Y, Pennell ML, Pearl DK, Knobloch TJ, Fernandez S, and Weghorst CM. The choice of reference gene affects statistical efficiency in quantitative PCR data analysis. Biotechniques 55(4):207–209. 2013. PMID: 24107253

Casto BC, Knobloch TJ, Galioto RL, Yu Z, Accurso BT, Warner BM. Chemoprevention of oral cancer by lyophilized strawberries. Anticancer Res. 2013 Nov;33(11):4757-66. PMID: 24222110

Poi MJ, Knobloch TJ, Yuan C, Tsai MD, Weghorst CM, Li J. Evidence that P12, a specific variant of P16(INK4A), plays a suppressive role in human pancreatic carcinogenesis. Biochem Biophys Res Commun. 2013 Jun 28;436(2):217-22. PMID: 23727582

2012 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Pereira MA, Warner BM, Knobloch TJ, Weghorst CM, Lubet RA, Steele VE, and Casto BC. Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid and atorvastatin. Int J Cancer 131(6):1277–1286, 2012. PMID: 22161747

Li J, Knobloch TJ, Poi MJ, Zhang Z, Davis AT, Muscarella P, Weghorst CM. Genetic alterations of RD(INK4/ARF) enhancer in human cancer cells. Mol Carcinog. 2014 Mar;53(3):211-8. PMID: 23065809

2011 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Li J, Knobloch TJ, Kresty LA, Zhang Z, Lang JC, Schuller DE, and Weghorst CM. Gankyrin, a biomarker for epithelial carcinogenesis, is overexpressed in human oral cancer. Anticancer Res 31(9):2683–2692, 2011. PMID: 21868508 **[Comment: Authors Li and Knobloch contributed to this work equally]

Zhang Z, Knobloch TJ, Seamon LG, Stoner GD, Cohn DE, Paskett ED, Fowler JM, and Weghorst CM. A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells. Gynecol Oncol 123(2):401–406, 2011. PMID: 21831414

Accurso BT, Warner BM, Knobloch TJ, Weghorst CM, Shumway BS, Allen CM, and Kalmar JR. Allelic imbalance in oral lichen planus and assessment of its classification as a premalignant condition. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112(3):359–366, 2011. PMID: 21764610 **[Comment: American Academy of Oral & Maxillofacial Pathology, Best Paper in Oral Pathology Award, 2012]

2009 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Casto BC, Sharma S, Fisher JL, Knobloch TJ, Agrawal A, and Weghorst CM. Oral cancer in Appalachia. J Health Care Poor Underserved 20(1):274–285, 2009. PMID: 19202262

Nam J, Rath B, Knobloch T, Lannutti J, and Agarwal S. Novel Electrospun Scaffolds for the Molecular Analysis of Chondrocytes under Dynamic Compression. Tissue Eng Part A 15(3):513–523, 2009. PMID: 18694324

2008 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Kresty LA, Mallery SR, Knobloch TJ, Song H, Lloyd M, S Zwick, Casto BC and Weghorst CM. Frequent alterations of p16INK4a and p14ARF in oral proliferative verrucous leukoplakia. Cancer Epidemiol Biomarkers Prev 17(11):3179–3187, 2008. PMID: 18990760

Li J, Warner B, Casto BC, Knobloch TJ, and Weghorst CM. Tumor suppressor p16(INK4A)/Cdkn2a alterations in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster cheek pouch tumors. Mol Carcinog 47(10):733–738., 2008. PMID: 18247379

Anghelina M, Sjostrom D, Perera P, Nam J, Knobloch T, and Agarwal S. Regulation of biomechanical signals by NF-kappaB transcription factors in chondrocytes. Biorheology 45(3–4):245–256, 2008. PMID: 18836228

Rath B, Nam J, Knobloch TJ, Lannutti JJ, and Agarwal S. Compressive Forces Induce Osteogenic Gene Expression In Calvarial Osteoblasts. J Biomech 41(5):1095–1103, 2008. PMID: 18191137

Knobloch TJ, Madhavan S, Nam J, Agarwal SK, and Agarwal S. Regulation of Chondrocytic Gene Expression by Biomechanical Signals. Crit Rev Eukaryot Gene Expr 18(2):139–150, 2008. PMID: 18304028

2007 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Bian Y, Knobloch TJ, Sadim M, Kaklamani V, Raji A, Yang GY, Weghorst CM, and Pasche B. Somatic Acquisition of TGFBR1*6A by Epithelial and Stromal Cells During Head and Neck and Colon Cancer Development. Hum Mol Genet 16(24): 3128–3135. 2007.PMID: 17890272

Dossumbekova A, Anghelina M, Madhavan S, He L, Quan N, Knobloch T, Agarwal S. Biomechanical Signals Inhibit IKK Activity to Attenuate NF-kappaB Transcription Activity in Inflamed Chondrocytes. Arthritis Rheum 56(10):3284–3296, 2007. PMID: 17907174 **[Comment in Arthritis Rheum 56(10):3176–3179, 2007. Oegema TR. Molecular basis of the interaction of inflammation and exercise: keep on walking! ]

Chandran R, Knobloch TJ, Anghelina M, and Agarwal S. Biomechanical Signals Upregulate Myogenic Gene Induction in the Presence or Absence of Inflammation. Am J Physiol Cell Physiol 293(1):C267–C276, 2007. PMID: 17392379

2005 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Pasche B, Knobloch TJ, Bian Y, Liu J, Phukan S, Rosman D, Kaklamani V, Baddi L, Frankel W, Prior TW, Schuller DE, Agrawal A, Lang JC, Dolan ME, Vokes EE, Lane WS, Huang C-C, Caldes T, Di Cristofano A, Hampel H, Nilsson IM, von Heijne G, Fodde R, Murty VVVS, de la Chapelle A, and Weghorst CM. Somatic Acquisition and Signaling of TGFBR1*6A in Cancer. JAMA 294(13):1634–1646, 2005. PMID: 16204663

Li J, Muscarella P, Joo SH, Knobloch TJ, Melvin WS, Weghorst CM and Tsai MD. Dissection of CDK4-Binding and Transactivation Activities of p34(SEI)(-)(1) and Comparison between Functions of p34(SEI)(-)(1) and p16(INK4A). Biochemistry 44(40):13246–13256. 2005. PMID: 16201750

2004 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Li J, Weghorst CM, Tsutsumi M, Poi MJ, Knobloch TJ, Casto BC, Melvin WS, Tsai M-D and Muscarella P. Frequent p16INK4A/CDKN2A alterations in chemically induced Syrian golden hamster pancreatic tumors. Carcinogenesis 25(2):263–268, 2004. PMID: 14604895

2003 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Li J, Qin D, Knobloch TJ, Tsai M-D, Weghorst CM, Melvin WS and Muscarella P. Expression and characterization of Syrian Golden hamster p16, a homologue of human tumor suppressor p16INK4A. Biochem Biophys Res Commun 304(2):241–247, 2003. PMID: 12711305

2002 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Casto BC, Kresty LA, Kraly CL, Pearl DK, Knobloch TJ, Schut HA, Stoner GD, Mallery SR, and Weghorst CM. Chemoprevention of oral cancer by black raspberries. 2002. Anticancer Res 22(6C):4005–4016, 2002. PMID: 12553025

Kresty LA, Mallery SR, Knobloch TJ, Song H, Lloyd M, Casto BC, and Weghorst CM. Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial dysplasia. Cancer Res 62(18):5295–5300, 2002. PMID: 12234999

2001 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Muscarella P, Knobloch TJ, Ulrich AB, Casto BC, Moniaux N, Wittel UA, Melvin WS, Pour PM, Song H, Gold B, Batra SK, and Weghorst CM. Identification and sequencing of the Syrian golden hamster (Mesocricetus auratus) p16INK4a and p15INK4b cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells. Gene 278(1–2):235–243, 2001. PMID: 11707341

Knobloch TJ, Lynch MA, Song H, DeGroff VL, Casto BC, Adams EM, Alam KY, Lang JC, Schuller DE, and Weghorst CM. Analysis of TGF-β type I receptor for mutations and polymorphisms in head and neck cancers. Mutat Res 479(1–2):131–139, 2001. PMID: 11470488

Lynch MA, Petrel TA, Song H, Knobloch TJ, Casto BC, Ramljak D, Anderson LM, DeGroff V, Stoner GD, Brueggemeier RW, and Weghorst CM. Responsiveness to transforming growth factor-beta (TGF-beta)-mediated growth inhibition is a function of membrane-bound TGF-beta type II receptor in human breast cancer cells. Gene Expr 9(4–5):157–171, 2001.

1997 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Kenny JJ, Knobloch TJ, Augustus M, Carter KC, Rosen CA, and Lang JC. GRS, a novel member of the BCL2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes. Oncogene 14(8):997–1001, 1997. PMID: 9050999

Dayton MA and Knobloch TJ. Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung fibroblast cell line WI-38. Recept Signal Transduct 7(4):241–256, 1997.

Lang JC, Tobin EJ, Knobloch TJ, Schuller DE, Mountain RE, Nicholson R, DeYoung BR, Weghorst CM. Frequent mutation of p16 in squamous cell carcinoma of the head and neck. Laryngoscope 108(6):923–928, 1997. PMID: 9628511

1996 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Lucas JM, Knobloch TJ, and Lang JC. Expression of the fibroblast growth factor 4 (FGF-4) gene is regulated by serum in Tera2 embryonal carcinoma cells. Int J Oncol 8:377–381, 1996. PMID: 21544372

1995 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Bryans M, Lucas JM, Knobloch TJ, Wilkie NM, and Lang JC. Regulation of FGF4 enhancer activity by transcription factor NFY. Biochem Biophys Res Commun 211(2):519–527, 1995. PMID: 7794264

Sharma V, Knobloch TJ, and Benjamin D. Differential expression of cytokine genes in HIV-1 TAT transfected T-cell and B-cell lines. Biochem Biophys Res Comm 208(2):704–713, 1995. PMID: 7695626

1994 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Benjamin D, Sharma V, Knobloch TJ, Armitage RJ, Dayton MA, and Goodwin RG. B-cell IL 7: human B-cell lines constitutively secrete IL 7 and express IL 7 receptors. J Immunol 152(10):4749–4757, 1994. PMID: 8176200

1992 ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Benjamin D, Knobloch TJ, and Dayton MA. Human B-cell interleukin 10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin 10. Blood 80(5):1289–1298, 1992. PMID: 1325212 [ Comment in Blood 81(4):1106–1107, 1993. Emilie D, Galanaud P, Raphael M, Joab I. Interleukin-10 and acquired immunodeficiency syndrome lymphomas. ]

Dayton MA, Knobloch TJ, and Benjamin D. Human B-cell lines express the interferon gamma gene. Cytokine 4(6):454–460, 1992. PMID: 1292629

BOOK CHAPTERS –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Knobloch TJ, Casto BC, Agrawal A, Clinton SK, and Weghorst CM. Cancer Prevention in Populations High At-Risk for the Development of Oral Cancer: Clinical Trials with Black Raspberries; Editors Stoner GD and Seeram NP. Berries and Cancer Prevention. New York, NY: Springer New York; 2010. p. 259–280.

Casto BC, Knobloch TJ, and Weghorst CM. Inhibition of Oral Cancer in Animal Models by Black Raspberries and Berry Components; Editors Stoner GD and Seeram NP. Berries and Cancer Prevention. New York, NY: Springer New York; 2010. p. 189–207.

INVITED REVIEWS –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Knobloch TJ, Madhavan S, Nam J, Agarwal SK, and Agarwal S. Regulation of Chondrocytic Gene Expression by Biomechanical Signals. Crit Rev Eukaryot Gene Expr 18(2):139–150, 2008. PMID: 1830402