Associate Professor – PracticeComprehensive Cancer Center – Molecular Carcinogenesis and Chemoprevention ProgramCenter for Advanced Function Foods & Entrepreneurship – Food Innovation CenterOSU COVID19 Case Investigation and Contact Tracing Team (CICTT)
"Beyond mountains there are mountains," was spoken to Dr. Paul Farmer as he fought tuberculosis in the health dispaired, underserved, and marginalized people in Haiti.
Mountains Beyond Mountains: The Quest of Dr. Paul Farmer, A Man Who Would Cure the World by Tracy Kidder (2003.)
This Haitian proverb reminds us that as one problem is solved, another will present itself, and then we must solve that one too.
"We can't solve problems by using the same kind of thinking we used when we created them," is paraphrased from several quotes by physicist Albert Einstein. If we are not prepared to think different, sometimes radically, then we are destined to repeat our failures.
knobloch [dot] 1osu [dot] edu
I 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 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 Internal Medicine physician scientist (Mark A. Dayton, PhD, MD) in the Division of Hematology & Oncology in the Department of Internal Medicine within the College of Medicine & Public Health.
I returned to graduate school and joined the research group of Jas Campbell Lang, Ph.D. 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 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 cancer prevention tools. This emerging science of black raspberry-mediated cancer chemoprevention was spearheaded by fundatmental studies by Gary D. Stoner, Ph.D., and would eventually shape the next 25 years of my research efforts.
Gaining experience as a Research 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. These cyanotoxins are associated with the promotion of liver cancer, and can bioaccumulated in fish (see how I circled back to fish!) that are eated, accumulated in plants consumed as fresh produce, and contaminate drinking water when processing facilities are overwhelmed by bloom surges. 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.
My research program includes several key interests:
1. Characterizing malignant molecular progression of epithelial carcinogenesis in cancers associated with tobacco smoking, alcohol consumtion, and HPV infections (oral cancers, cervical cancers).
2. The use of food-based interventions as implementable cancer risk-reduction strategies, with special emphasis on the bioactive phytochemicals present in black raspberries.
3. The emerging role of bacterial cyanotoxins released during harmful algal blooms in the promotion of liver cancer in susceptible populations.
4. Investigating the knowledge gap surrounding effective harm reduction and reducing cancer risk in firefighting personnel.
My work is fundamentally translational in nature and emphasizes the integrated participation of genomic (epigenetic, SNPs), transcriptional (expression signatures), metabolic (bioactive signaling cascades), and microbiomic (host-bacterial ecosystems) landscapes
Mrdjen I, Lee J, Weghorst CM, Knobloch TJ. Impact of Cyanotoxin Ingestion on Liver Cancer Development Using an At-Risk Two-Staged Model of Mouse Hepatocarcinogenesis. Toxins (Basel). 2022 Jul 14;14(7):484. doi: 10.3390/toxins14070484.PMID: 35878222
Mills MC, Evans MV, Lee S, Knobloch T, Weghorst C, Lee J. Acute cyanotoxin poisoning reveals a marginal effect on mouse gut microbiome composition but indicates metabolic shifts related to liver and gut inflammation. Ecotoxicol Environ Saf. 2021 Jun 1;215:112126. doi: 10.1016/j.ecoenv.2021.112126. Epub 2021 Mar 13. PMID: 33721663
Cosby LE, Lee KH, Knobloch TJ, Weghorst CM, Winter JO. Comparative Encapsulation Efficiency of Lutein in Micelles Synthesized via Batch and High Throughput Methods. Int J Nanomedicine. 2020 Oct 23;15:8217-8230. doi: 10.2147/IJN.S259202. eCollection 2020. PMID: 33122907
Lee J, Lee S, Mayta A, Mrdjen I, Weghorst C, Knobloch T. Microcystis toxin-mediated tumor promotion and toxicity lead to shifts in mouse gut microbiome. Ecotoxicol Environ Saf. 2020 Dec 15;206:111204. doi: 10.1016/j.ecoenv.2020.111204.
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. 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
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. PMID: 31229487
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
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. PMID: 30288460
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
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
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
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
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
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
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 *[Comment: Authors Li and Knobloch contributed to this work equally]
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]
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
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
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
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
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
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
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
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.
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
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
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
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
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