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Gerry Boss Laboratory

A message from Dr. Boss

I have combined primary care internal medicine with basic laboratory research throughout my career.  Although to many physicians this may seem a strange combination, the two areas of work complement each other well.  Laboratory work is characterized by delayed gratification, sometimes delayed to the point of wanting to give up, whereas primary care can provide an immediate sense of fulfillment, even though many frustrations can arise in delivering high-quality care.  Moreover, basic science research should not be the purview of only subspecialists.  There is no reason why primary care should not be able to pursue basic laboratory work.  It should also be noted that basic science transcends medical specialties and one does not have to be a cardiologist or nephrologist to study transduction pathways in cardiomyocytes or renal tubular epithelial cells. 

I have worked in different areas from regulation to carbon flow through the folate pathway to Ras/MAP kinase signaling.  I currently have two major research activities.  The first is developing the vitamin B12 analog cobinamide as a new therapy for poisoning by multiple toxic chemicals as well as radiation-induced cell damage.  Cobinamide has a very high affinity for cyanide and free radicals, and acts as a scavenger of these toxic chemicals.  Much of the detrimental effects of radiation are mediated via free radicals.  As a vitamin B12 analog, cobinamide is relatively non-toxic, and we have had several pre-Investigators New Drug (IND) meetings with the Food and Drug Administration.  We hope to be in clinical trials sometime in 2023. 

The second major area of research is studying the regulation of purine nucleotide synthesis by amino acid availability and the phosphatidylinosol 3-kinase/Akt pathway.  We have found that amino acids are potent regulators of purine nucleotide synthesis, and that Akt phosphorylates transketolase, a key enzyme in the non-oxidative pentose phosphate pathway that supplies ribose sugars for purine synthesis.  As part of these studies, the lab has found that purine synthesis is regulated during the cell cycle.  This work could lead to novel forms of cancer treatment since purines are required for DNA and RNA synthesis and cellular metabolism. 

In my laboratory, there are currently two Project Scientists, two postdoctoral fellows, one graduate student, and two research technicians.  In addition, I collaborate closely with another physician-scientist faculty member. 

Publications Since 2017 

  1. Kambale KJ, Ali ER, Sadiki NH, Kayembe KP, Mvumbi LG, Yandju DL, Boivin MJ, Boss GR, Stadler DD, Lambert WE, Lasarev MR, Okitundu LA, Mumba Ngoyi D, Banea JP, Tshala-Katumbay DD. Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning. Neurotoxicology. 2017; 59:256-262. PubMed PMID: 27246648; PubMed Central PMCID: PMC5125906.
  2. Tsai CS, Mao RW, Tsai SC, Shahverdi K, Zhu Y, Lin SK, Hsu YH, Boss G, Brenner M, Mahon S, Smaldone GC. Faraday Waves-Based Integrated Ultrasonic Micro-Droplet Generator and Applications. Micromachines (Basel). 2017; 8(2), 56. PubMed PMID: 29250438; PubMed Central PMCID: PMC5726552.
  3. Kalyanaraman H, Ramdani G, Joshua J, Schall N, Boss GR, Cory E, Sah RL, Casteel DE, Pilz RB.  A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice. J Bone Miner Res. 2017; 32(1):46-59 PubMed PMID: 27391172; PubMed Central PMCID: PMC5199609
  4. Bebarta VS, Brittain M, Chan A, Garrett N, Yoon D, Burney T, Mukai D, Babin M, Pilz RB, Mahon SB, Brenner M, Boss GR. Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection. Ann Emerg Med. 2017; 69: 718-725. PubMed PMID: 28041825.
  5. Nath AK, Shi X, Harrison DL, Morningstar JE, Mahon S, Chan A, Sips P, Lee J, MacRae CA, Boss GR, Brenner M, Gerszten RE, Peterson RT. Cisplatin Analogs Confer Protection against Cyanide Poisoning. Cell Chem Biol. 2017; 24: 565-575. PubMed PMID: 28416275.
  6. Bebarta VS, Garrett N, Brenner M, Mahon S, Maddry JK, Boudreau S, Castaneda M, Boss GR. Efficacy of intravenous cobinamide versus hydroxocobalamin or saline for treatment of severe hydrogen sulfide toxicity in a swine (Sus Scrofa) model. Acad Emerg Med. 2017; 24(9):1088-1098 PMID: 28472554
  7. Brenner M, Azer SM, Oh KJ, Han CH, Lee J, Mahon SB, Du X, Mukai D, Burney T, Saidian M, Chan A, Straker DI, Bebarta VS, Boss GR. Oral Glycine and Sodium Thiosulfate for Lethal Cyanide Ingestion. J Clin Toxicol. 2017; 7(3).355. doi: 10.4172/2167-7972. 1000355. PMID: 28868209
  8. Greenawald LA, Boss GR, Snyder JL, Reeder A, Bell S.  Development of an Inexpensive RGB Color Sensor for the Detection of Hydrogen Cyanide Gas. ACS Sensors. 2017; 2 (10):1458-1466. PMID: 28967741.
  9. Anantharam P, Whitley EM, Mahama B, Kim DS, Sarkar S, Santana C, Chan A, Kanthasamy AG, Kanthasamy A, Boss GR, Rumbeiha WK. Cobinamide is effective for treatment of hydrogen sulfide-induced neurological sequelae in a mouse model. Ann N Y Acad Sci. 2017; 1408(1):61-78. PubMed PMID: 29239480; PubMed Central PMCID: PMC5734662.
  10. Sips PY, Shi X, Musso G, Nath AK, Zhao Y, Nielson J, Morningstar J, Kelly AE, Mikell B, Buys E, Bebarta V, Rutter J, Davisson VJ, Mahon S, Brenner M, Boss GR, Peterson RT, Gerszten RE, MacRae CA. Identification of specific metabolic pathways as druggable targets regulating the sensitivity to cyanide poisoning. PLoS One. 2018; 13(6):e0193889. doi: 10.1371/journal.pone.0193889. PubMed PMID: 29879736; PubMed Central PMCID: PMC5991913.
  11. Ng PC, Hendry-Hofer TB, Witeof AE, Brenner M, Mahon SB, Boss GR, Bebarta VS. Characterization of a Swine (Sus scrofa) Model of Oral Potassium Cyanide Intoxication. Comp Med. 2018; 68:375-379. PubMed PMID: 30208987; PubMed Central PMCID: PMC6200030.
  12. Ng PC, Hendry-Hofer TB, Garrett N, Brenner M, Mahon SB, Maddry JK, Haouzi P, Boss GR, Gibbons TF, Araña AA, Bebarta VS. Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine. Clin Toxicol (Phila). 2019; 57:189-196. PubMed PMID: 30430872; PubMed Central PMCID: PMC6540978.
  13. Petrikovics I, Kiss L, Chou CE, Ebrahimpour A, Kovács K, Kiss M, Logue B, Chan A, Manage ABW, Budai M, Boss GR, Rockwood GA. Antidotal efficacies of the cyanide antidote candidate dimethyl trisulfide alone and in combination with cobinamide derivatives. Toxicol Mech Methods. 2019; 1:1-7. PubMed PMID: 30822191.
  14. Ng PC, Hendry-Hofer TB, Witeof AE, Mahon SB, Brenner M, Boss GR, Bebarta VS. Efficacy of Oral Administration of Sodium Thiosulfate and Glycine in a Large, Swine Model of Oral Cyanide Toxicity. Ann Emerg Med. 2019; 74:423-429.  PubMed PMID: 31080026.
  15. Morningstar J, Lee J, Hendry-Hofer T, Witeof A, Lyle LT, Knipp G, MacRae CA, Boss GR, Peterson RT, Davisson VJ, Gerszten RE, Bebarta VS, Mahon S, Brenner M, Nath AK. Intramuscular administration of hexachloroplatinate reverses cyanide-induced metabolic derangements and counteracts severe cyanide poisoning. FASEB Bioadv. 2019; 1:81-92. PubMed PMID: 31355359; PubMed Central PMCID: PMC6660183.
  16. Schwaerzer GK, Kalyanaraman H, Casteel DE, Dalton ND, Gu Y, Lee S, Zhuang S, Wahwah N, Schilling JM, Patel HH, Zhang Q, Makino A, Milewicz DM, Peterson KL,Boss GR, Pilz RB. Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B12 analog. Nat Commun. 2019; 10:3533. PubMed PMID: 31387997; PubMed Central PMCID: PMC6684604.
  17. Hendry-Hofer TB, Ng PC, McGrath AM, Mukai D, Brenner M, Mahon S, Maddry JK, Boss GR, Bebarta VS. Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model. Ann N Y Acad Sci. 2020; 1479: 159-167. PMID: 32233102.
  18. Hendry-Hofer TB, Witeof AE, Ng PC, Mahon SB, Brenner M, Boss GR, Bebarta VS. Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity. Clin Toxicol (Phila). 2020; 58:29-35. PubMed PMID: 31008657; PubMed Central PMCID: PMC7521135.
  19. Tat J, Hays B, Teachworth M, Kuo A, Pilz RB, Golomb BA, Boss GR. Assessment of High School Students' Participation in Blood Donation and Registration as an Organ Donor. JAMA Network Open. 2020; 3:e2016377. PubMed PMID: 32945872; PubMed Central PMCID: PMC7501534.
  20. Wahwah N, Dhar D, Chen H, Zhuang S, Chan A, Casteel DE, Kalyanaraman H, Pilz RB, Boss GR. Metabolic interaction between amino acid deprivation and cisplatin synergistically reduces phosphoribosyl-pyrophosphate and augments cisplatin cytotoxicity. Sci Rep. 2020; 10(1):19907. PMID: 33199755.
  21. Hendry-Hofer TB, Ng PC, McGrath AM, Soules K, Mukai DS, Chan A, Maddry JK, White CW, Lee J, Mahon SB, Brenner M, Boss GR, Bebarta VS. Intramuscular cobinamide as an antidote to methyl mercaptan poisoning. Inhal Toxicol. 2021 33:25-32. PMID: 33356664.
  22. Lu YS, Vijayakumar S, Chaix A, Pimentel BR, Bentz KC, Li S, Chan A, Wahl C, Ha JS, Hunka DE, Boss GR, Cohen SM, Sailor MJ. Remote Detection of HCN, HF, and Nerve Agent Vapors Based on Self-Referencing, Dye-Impregnated Porous Silicon Photonic Crystals.  ACS Sens. 2021; 6:418-428. PMID: 33263399.
  23. Ng PC, Hendry-Hofer TB, Brenner M, Mahon SB, Boss GR, Maddry JK, Bebarta VS. Efficacy of oral administration of sodium thiosulfate in a large, swine model of oral cyanide toxicity. J Med Toxicol. 2021. 17:257-264. PMID: 33821433.
  24. Schwaerzer GK, Casteel DE, Cividini F, Kalyanaraman H, Zhuang S, Gu Y, Dalton ND, Peterson KL, Dillmann WH, Boss GR, Pilz RB. Constitutive protein kinase G activation exacerbates stress-induced cardiomyopathy.  Br J Pharmacol. 2021 May 17. doi: 10.1111/bph.15530. Online ahead of print. PMID: 34000062.
  25. Sahu D, Huan J, Wang H, Sahoo D, Casteel DE, Klemke RL, Boss GR, Hansel DE. Bladder Cancer Invasion Is Mediated by Mammalian Target of Rapamycin Complex 2-Driven Regulation of Nitric Oxide and Invadopodia Formation. Am J Pathol. 2021 Aug 21:S0002-9440(21)00350-3. doi: 10.1016/j.ajpath.2021.08.002. Epub ahead of print. PMID: 34428425.
  26. Chan A, Lee J, Bhadra S, Bortey-Sam N, Hendry-Hofer TB, Bebarta VS, Mahon SB, Brenner M, Logue B, Pilz RB, Boss GR. Development of sodium tetrathionate as a cyanide and methanethiol antidote. Clin Toxicol (Phila). 2021 Jul 30:1-10. doi: 10.1080/15563650.2021.1953517. Epub ahead of print. PMID: 34328378.
  27. Tat J, Heskett K, Satomi S, Pilz R, Golomb BA, Boss GR 2021. Sodium azide poisoning: a narrative review.  Clin. Toxicol (Phila) 2021. 59:683-697. doi: 10.1080/15563650.2021.1906888. PMID: 34128439.
  28. Philipopoulos GP, Tat J, Chan A, Jiang J, Mukai D, Burney T, Doosty M, Mahon S, Patel HH, White CW, Brenner M, Lee J, Boss GR.   Methyl mercaptan gas: mechanisms of toxicity and demonstration of the effectiveness of cobinamide as an antidote in mice and rabbits. Clin Toxicol (Phila). 2022 Jan 6:1-8. doi: 10.1080/15563650.2021.2017949. Online ahead of print.PMID: 34989638.