Pinto, John (jp904)

John Pinto

Adjunct Full Professor

Office Location:

532B Building 528

Educational Background

B.S. (Chemistry), St. John Fisher College, Rochester, NY, 1968
Ph.D., (Biochemistry), University of Medicine and Dentistry of NJ, 1974
Post-doctoral studies (Nutrition), Columbia University, 1975-78

Scholarly Interests

Anticancer effects of organoselenium, organsulfur, and polyphenolic compounds; Chemoprotective mechanisms of phytonutrients and plant extracts on human health and disease; and Interactions of drugs, xenobiotics and nutrients.

Selected Publications

CHAPTERS IN BOOKS: 2015-2022 (Life time chapters published 17)

Pinto JT and Rivlin RS. Riboflavin. IN: Handbook of Vitamins. Nutritional, Biochemical, and Clinical Aspects. Gregory J, Stover P, Suttie JW and Zempleni J, eds. (New York, Taylor and Francis, Inc., Fifth Edition), Chapter 6: pp 192-265, 2014.  ISBN:  13:978-1-4665-1556-7

Aquilato A, Lopez V, Doonan B, Hsieh T-C, Pinto JT, Wu E and  Wu JM.  BRAF Mutation in Melanoma and Dietary Polyphenols as Adjunctive Treatment Strategy. Chapter 102. IN: Polyphenols in Human Health and Disease: Vol 2; Watson RR, Preedy VR, and Zibadi S. eds. (Elsevier: San Diego, CA,) pp. 1353-1365, 2013. 

Cooper AJL, Dorai T, Dorai B, Krasnikov BF, Li JY, Hallen A, and Pinto JT.  Role of glutamine transaminases in nitrogen, sulfur, selenium and 1-carbon metabolism.  Chapter 3, pp. 37-54, IN: Glutamine in Clinical Nutrition.  Rajendram R, Preedy VR, and Patel VB. (Eds.) (Humana Press, New York) 2015.  

Pinto JT, Hsieh TC, Wu JM.  Genomic and nongenomic controls of vitamin D on cardiovascular health and disease. Chapter 5, pp 91-112. IN: Handbook of nutrition in heart health.  Ronald Watson, Ph.D. and Sherma Zibadi, M.D., Ph.D., (Eds). Wageningen Academics, Wageningen Academic Publishers, (Netherlands), 2017.

Pinto JT, Hsieh TC, Brown S, Madrid J, Wu JM.  Advances on effects of copper on cardiovascular health.Chapter 10, pp 213-228.  IN: Handbook of nutrition in heart health.  Ronald Watson, Ph.D. and Sherma Zibadi, M.D., Ph.D., (Eds). Wageningen Academics, Wageningen Academic Publishers, (Netherlands), 2017.

Schaafsma E., Pinto J, Garvey J, Garvey R, Wu JM, Hsieh T-C.  Evolution from Gene to Gene Network: Using Bioinformatics to Gain Insights into Chemopreventive Mechanism of Resveratrol. Chapter 12, pp 309-328. IN: Resveratrol: State-of-the-art science and health applications; Joseph M. Wu, Tze-chen Hsieh (Eds). (World Scientific Publishing Co, Inc. Hackensack, N.J.), 2019.

JOURNAL ARTICLES PUBLISHED IN 2015-2022 (Life time publication 139 peer-reviewed manuscripts)

Pinto JT, Cooper AJL.  From cholesterogenesis to steroidogenesis: Role of riboflavin and flavoenzymes in the biosynthesis of vitamin D.  Adv Nutr 5: 144-163, 2014. PMID: 24618756. PMCID: PMC3951797.

Csiszar A, Csiszar A, Pinto JT, Gautam T, Kleusch C, Hoffmann B, Tucsek Z, Toth P, Sonntag WE, Ungvari Z. Resveratrol encapsulated in novel fusogenic liposomes activates Nrf2 and attenuates oxidative stress in cerebromicrovascular endothelial cells from aged rats. J Gerontol A Biol Sci Med Sci. 70(3):303-13. 2015. PMID:24642904.

Sinha I, Allen JE, Pinto JT, and Sinha R. Methylseleninic acid elevates REDD1 and inhibits prostate cancer cell growth despite AKT activation and mTOR dysregulation in hypoxia. Cancer Med. 3(2): 252-264, 2014. PMID: 24515947. PMCID: PMC3987075.

Vauzour D, Pinto JT, Cooper AJL, Spencer JPE. The neurotoxicity of 5-S-cysteinyldopamine is mediated by the early activation of ERK1/2 followed by the subsequent activation of ASK-1/JNK1/2 pro-apoptotic signalling.  Biochem J. 463(1): 41-52, 2014. PMID:24938188.

Pinto JT, Krasnikov BF, Alcutt S, Jones ME, Dorai T, Villar MT, Artigues A, Li J, Cooper AJL. Kynurenine aminotransferase III and glutamine transaminase L are identical enzymes that have cysteine S-conjugate β-lyase Activity and can transaminate L-selenomethionine.  J Biol Chem. 289(45), 30950-30961, 2014. PMID:25231977.

Kang Y, Nian H, Rajendran P, Kim E, Dashwood WM, Pinto JT, Boardman LA, Thibodeau SN, Limburg PJ, Löhr CV, Bisson WH, Williams DE, Ho E, Dashwood RH. HDAC8 and STAT3 repress BMF gene activity in colon cancer cells. Cell Death Disease 5(10): e1476, 2014. PMID: 25321483.

Sleiman SF, Olson DE, Bourassa MW, Karuppagounder SS, Zhang YL, Gale J, Wagner FF, Basso M, Coppola G, Pinto JT, Holson EB, Ratan RR. Hydroxamic based histone deacetylase (HDAC) inhibitors can mediate neuroprotection independent of HDAC inhibition. J Neurosci. 34(43):14328 –14337, 2014. PMID:25339746

Huang A, Pinto JT, Froogh G, Kandhi S, Qin J, Wolin MS, Hintze TH, Sun D. A role of homocysteinylation of ACE in endothelial dysfunction of arteries.  Am J. Physiol., Heart Circ Physiol. 308(2):H92-H100, 2015. PMID: 25416191

Weston RE, Weston PJ, Futterman RF, Lepore SJ, Carolina DS, Pinto JT, Lang MA, Thomas RI, Cardwell JJ, Gordon AP. Effectiveness of a Modified Computer Assisted Instructional Tool In The Dissemination of Prostate Cancer Information to Men of African Descent Through Black Churches. J Afr Amer Studies 11(2):140-156. 2007.

Cooper AJL, Shurubor YI, Dorai T, Pinto JT, Isakova EP, Deryabina YI, Denton TT, Krasnikov BF. ω-Amidase – An underappreciated, but important enzyme in L-glutamine and L-asparagine metabolism in mammals.  Amino Acids.  48(1):1-20, 2016. Review. Erratum in: Amino Acids. 47(12):2671-2, 2015. PMID: 26259930

Pinto JT, Zempleni J. Riboflavin.  Adv Nutr.  7(5):973-975, 2016. PMID: 27633112

Dorai T, Pinto JT and Cooper AJL. Sweetening of glutamine metabolism in cancer cells by Rho GTPases through convergence of multiple oncogenic signaling pathways. Transl Cancer Res; 5(S2):S349-S356, 2016.

Schaafsma E, Hsieh T, Doonan BB, Pinto JT, Wu JM. Anticancer Activities of Resveratrol in Colorectal Cancer. Biol Med (Aligarh) 8(5): 217, 2016. doi:10.4172/0974-8369.1000317

Wu JM, Oraee A, Doonan BB, Pinto JT, Hsieh TC. Activation of NQO1 in NQO1*2 polymorphic human leukemic HL-60 cells by diet-derived sulforaphane. Exp Hematol Oncol. 5(1):27, 2016.  PMID: 27625902

Jeitner TM, Kristoferson E, Azcona JA, Pinto JT, Stalnecker C, Erickson JW, Kung HF, Li J, Ploessl K, and Cooper AJL. Fluorination at the 4 position alters the substrate behavior of L-glutamine and L-glutamate: Implications for positron emission tomography of neoplasias. J Fluor Chem. 192(A):58-67, 2016. PMID: 28546645

Froogh G, Pinto JT, Le Y, Kandhi S, Aleligne Y, Huang A and Sun D. Chymase-dependent production of angiotensin II: an old enzyme in old hearts.  Am J Physiol Heart Circ Physiol. 312(2):H223-H231, 2017 PMID: 27815252

Doonan BD, Schaafsma E, Pinto JT, Wu JM, and Hsieh T-C. Application of open-access databases to determine functional connectivity between resveratrol-binding protein QR2 and colorectal carcinoma.  In Vitro Cell Dev Biol Anim. 53:575-578, 2017.  Epub 2017 Jun 23. PMID: 28646291.

Nichenametla SN, Mattocks DAL, Malloy VL, and Pinto JT. Sulfur amino acid restriction-induced changes in redox-sensitive proteins are associated with slow protein synthesis rates. Ann N Y Acad Sci. 1418(1):80-94, 2018. PMID: 29377163

Jeitner T, Pinto JT, and Cooper AJL. Cystamine or cysteamine as inhibitors of transglutaminases in vivo. Biosci Rep. 2018 Sep 5; 38(5), 2018.  PMID: 30054429

Karuppagounder SS, Alin L, Chen YX, Brand D, Bourassa MW, Dietrich K, Wilkinson CM, Nadeau CA., Kumar A, Perry S, Pinto JT, Darley-Usmar V, Sanchez S, Milne GL, Pratico D, Holman TR, Carmichael ST, Coppola G, Colbourne F, and Ratan RR. N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize with PGE2 to inhibit ferroptosis and improve outcomes following hemorrhagic stroke in mice.  Ann Neurol. 84(6):854-872, 2018.

Dorai T, Dorai B, Pinto JT, Grasso M, Cooper AJL. High Levels of Glutaminase II Pathway Enzymes in Normal and Cancerous Prostate Suggest a Role in 'Glutamine Addiction'. Biomolecules 10(1):2 2019.

Dorai T, Pinto JT, Travis T. Denton TT, Krasnikov BF, Cooper AJL. The Metabolic Importance of the Glutaminase II Pathway in Normal and Cancerous Cells. Anal Biochem. 2020 Dec 19:114083.

Cooper AJL, Dorai T, Pinto JT, Denton TT. The Metabolic Importance of the Overlooked Asparaginase II Pathway. Anal Biochem. 2020 Dec 22:114084.

Kumar A, Vaish M, Karuppagounder SS, Gazaryan I, Cave JW, Starkov AA, Anderson ET, Zhang S, Pinto JT, Rountree A, Wang W, Sweet IR, Ratan RR. HIF1α stability in hypoxia is not oxidant-initiated. Accepted for publication; eLife 2021;10:e72873. DOI:

John Thomas Pinto is Professor of Biochemistry and Molecular Biology at New York Medical College in Valhalla, New York. His training in Nutritional Biochemistry began in 1974 at the Institute of Human Nutrition, Columbia University. In 1980, he joined the staff at Memorial Sloan-Kettering Cancer Center (MSKCC) as Assistant Laboratory Member and was appointed Assistant Professor of Nutrition in Medicine, Weill Medical College of Cornell University in New York City.  During that time (1980-83), he was awarded the Future Leader's Award from the Nutrition Foundation. From 1989 until 1996, he co-directed the Metabolism and Oncology Core Laboratory within the Clinical Nutrition Research Unit (CNRU) at MSKCC and until 2002, also directed the Nutrition Research Laboratory.  In 2002 to 2004, he re-established the CNRU at the Institute for Cancer Prevention (Formerly, the American Health Foundation) until its closure and then joined the staff at the Cornell-Burke Medical Research Institute in White Plains, New York.  In 2007, he joined the faculty at New York Medical College in his current rank as Professor of Biochemistry and Molecular Biology.  His adjunct teaching appointments include Columbia University Teachers College in the Department of Health and Behavior Studies, The Institute of Human Nutrition (Columbia University), and the University of New Haven. He is a member of The American Institute of Nutrition, The American Society for Clinical Nutrition, and the American Association for Cancer Research.  Dr. Pinto serves as a reviewer for the American Journal of Clinical Nutrition, Nutrition and Cancer, the Journal of Nutrition, and Analytical Biochemistry.  His research focuses on identifying chemopreventive strategies for diminishing primary and secondary cancer risks. His particular investigations examine the effects of organosulfur, selenium and polyphenolic compounds on redox responsive metabolic pathways within human prostate, breast, and colon cancer cells. Dr. Pinto has identified epigenetic mechanisms by which these diet-derived constituents exert control over cell growth and proliferation through sulfhydryl-disulfide regulation of signal proteins, affecting transcription factors of gene expression, and inhibition of histone deacetylation. Histone deacetylase inhibitors are highly sought after agents that control diseases where inappropriate gene activation is a causal feature, namely viral replications and in cancer prevention and control.
Our research focuses on developing chemopreventive strategies for diminishing risk of developing primary and secondary cancers.  In particular, we investigate the effects of specific diet-derived phytonutrients upon oxidative and reductive metabolic pathways within human prostate and colon cancer cells.  Our goal is to characterize mechanisms by which diet-derived organoselenium and organosulfur constituents regulate cell growth and metabolism by modifying signal transduction pathways through sulfhydryl-disulfide regulation of proteins and inhibition of histone deacetylation.  Inhibitors of histone deacetylases are highly sought after compounds to control diseases where inappropriate gene activation is a causal feature, namely in cancer prevention and control.  This work is ongoing with collaborators at Penn State University, Oregon State University, and here at New York Medical College.

a.         Naturally-occurring organoselenium compounds
Our laboratory has identified mechanisms whereby naturally occurring organoselenium compounds exhibit chemopreventive effects on prostate and colon cancers.  We discovered novel metabolic conversions of diet-derived selenoamino acids, Se-methyl-L-selenocysteine (MSC) and L-selenomethionine (SM), to their respective selenoketo acid metabolites, methylselenopyruvate (MSP) and ketomethylselenobutyrate (KMSB).  Metabolism of MSC and SM and hence their chemopreventive qualities, were previously thought to occur primarily through β- and γ-lyase reactions.  The lyase pathways were hypothesized to generate highly reactive and short-lived, methylselenol, a metabolite that has not been measured nor identified to exist within tissues.  Our work shows that the selenoketo acids, derived from MSC and SM, but not MSC and SM themselves, exhibit potent inhibitory effects on a variety of histone deacetylases. This information has significantly altered our basic understanding of the chemopreventive activity associated with diet-derived organoselenium compounds.   We have also identified the specific transaminases responsible for the transamination of selenoamino acids to their corresponding keto acids as well as the selectivity of the tissue types capable transamination of each selenoamino acid.  Accordingly, glutamine transaminase K (kidney, GTK) selectively converts MSC to MSP and has less than 0.1% the activity with SM.  GTK is a ubiquitous enzyme and displays varying degrees of activity in various tissues. By contrast, glutamine transaminase L (Liver, GTL) selectively metabolizes SM to KMSB exhibiting much less activity toward MSC (5-10% that observed with SM).  This enzyme is present in liver and is marginally found in other tissues such as pancreas.  The significance of this information resides in issues surrounding the aborted nation-wide, clinical study SELECT.  Androgen responsive and non-responsive prostate cancer cells do not possess GTL but rather GTK and thus SM, which was provided to SELECT volunteers, was NOT effective in prostate cancer prevention perhaps for these reasons.  By contrast, prostate cells do exhibit adequate activity of GTK and thus would have exhibited a response if methylselenocysteine had been used.  This remains a viable issue and, in this investigator’s opinion, should evoke further studies. 

In both human prostate and colon cancer cells in culture, acetylated histone H3 levels increase during the period 5-24 h after treatment with direct addition of the selenoketo acids (MSP or KMSB).  The proportion of cells occupying G2/M phase of the cell cycle increases at 10-50 µM MSP and KMSB, and apoptosis is induced, as evidenced by morphological changes, Annexin V staining, and increased cleaved caspase-3, -6, -7-, -9, and poly(ADP-ribose)polymerase.  P21WAF1, a target used by investigators studying clinically-approved HDAC inhibitors, increases in MSP- and KMSB-treated colon cancer cells. Thus, in addition to targeting redox-sensitive signaling factors, selenoketo acids inhibit HDAC activity and nuclear status of acetylated histones.  

b.         Organoselenium compounds
In additional investigations on organoselenium compounds, we showed that another potential metabolite of methylselenocysteine promotes apoptosis in invasive prostate cancer cells in part by down regulating hypoxia inducible factor-1α (HIF-1α).  Accordingly, we demonstrate that methylseleninic acid activates or stabilizes REDD1 (Regulated in Development and DNA Damage Response 1), a conserved mitochondrial stress-response protein whose over-expression inhibits the mTOR (mammalian target of rapamycin) pathway, a critical regulator of tumor cell proliferation.  REDD1 has been suggested to act by binding to and sequestering 14-3-3 proteins away from tumor suppressor TSC2 (tuberous sclerosis complex subunit 2) thus leading to TSC2-dependent inhibition of the mTOR pathway.  Endogenous REDD1 is required for both dissociation of endogenous TSC2/14-3-3 and inhibition of mTORC1 in response to HIF-1α and hypoxia. Thus, methylseleninic acid activates REDD1 in metastatic prostate cancer cells and significantly inhibits expression of factors that activate the PI3K/PKB and mTOR/p70S6K1 signaling pathways even under hypoxic conditions.  In brief, phosphatidylinositol-3-kinase (PI3K) transmits a mitogenic signal through protein kinase B and mammalian target of rapamycin (mTOR) to p70S6K1. The mTOR inhibitor, rapamycin, is recognized to inhibit cells in G1 cell cycle progression and to block expression of cyclin D1, CDK4, CDC25A, and retinoblastoma phosphorylation. Our data suggest that methylseleninic induces REDD1 and inhibits prostate cancer cell growth in hypoxia despite activation of PKB and dysregulation of mTOR which are viable therapeutic targets in control of prostate cancer pathologies.

c.         Naturally-occurring organosulfur compounds
Our studies show that S-allylmercaptocysteine (SAMC), a garlic-derived compound, inhibits growth, arrests cells in G2/M, and induces apoptosis in LNCaP, LNCaP C4-2, and PC-3 human prostate carcinoma cells as well as in SW480 and HT29 human colon cancer cells.  Indirect immunofluorescent staining for microtubules (MTs) reveal that treatment of colon cancer cells or NIH3T3 fibroblasts with varying doses of SAMC causes MT depolymerization and MT cytoskeleton disruption in interphase cells, and interferes with the spindle assembly in mitotic cells.
Our investigations of signaling pathways involved in SAMC-induced apoptosis found that SAMC causes rapid and sustained induction of c-Jun NH2-terminal kinase-1 (JNK1) activity.  SAMC also activates caspase-3, as evidenced by the cleavage of a fluorogenic tetrapeptide substrate and of poly(ADP-ribose) polymerase. Conclusions thus far are that garlic-derived SAMC exerts anti-proliferative effects, at least in part, by disrupting MT assembly thus arresting cells in mitosis and triggering JNK1 and caspase-3 signaling pathways that lead to apoptosis. By investigating the regulatory role displayed by garlic-derived allylsulfides on expression of inducible redox sensitive signal proteins and enzymes and on the overall antioxidant potential of the cell, our studies summarize newly identified mechanisms by which garlic-derived allylsulfide constituents may contribute significantly to cancer prevention and control.

These studies provide novel paradigms by which diet-derived organoselenium and organosulfur compounds might protect against prostate, colon, and a variety of other cancers.
Back to skip to quick links