Markus Michael Bachschmid, PhD
Assistant Professor
Boston University School of Medicine
Dept of Medicine
Vascular Biology

PhD, Universität Konstanz
MS, Universität Konstanz



Redox regulation of metabolism by Sirtuin-1 and glutaredoxin-1 in the cardiovascular system and liver.

What is redox signaling?
The cellular redox status and oxidants play an important role in regulating cell physiology and signaling through oxidative protein modifications. Reactive cysteines (thiolates) in proteins can react with oxidants and abundant intracellular glutathione to form glutathione adducts. Glutaredoxins, also known as thioltransferases, remove protein glutathione adducts and restore the reactive state of cysteines. This sequence is part of a redox regulatory cycle, which modulates activities of many important proteins including transcription factors, central metabolic regulators, and signal transduction cascades. Oxidative stress in disease, however, interrupts this cycle and causes irreversible oxidation and inactivation of regulatory protein cysteines.


Clinical significance of redox signaling
Cellular redox homeostasis is perturbed in numerous diseases, dysregulating cellular signaling pathways and metabolic redox processes. Consequently, oxidative protein modifications increase and can serve as specific disease biomarkers. Better understandings of redox signaling and novel strategies for intervention are needed.
Current research in the Bachschmid lab focuses on specific redox signaling cascades and novel strategies I) to analyze protein oxidation, II) to prevent protein oxidation, III) to create oxidation resistant mutant proteins, and IV) to specifically inhibit proteins rendered dysfunctional by oxidants.


Genetic mouse model of redox signaling
The Bachschmid lab works with glutaredoxin-1 knockout mice, which exhibit increased protein glutathione adducts and develop obesity, dyslipidemia, fatty liver, and metabolic cardiovascular disease. We discovered three cysteine residues of sirtuin-1 modified with glutathione adducts, which inactivate this enzyme in glutaredoxin-1 knockout mice. Sirtuin-1 is a NAD-dependent protein deacetylase and central regulator of metabolism. Several metabolic diseases including non-alcoholic fatty liver and metabolic cardiovascular disease are associated with inactivation or decreased Sirtuin-1 expression. Glutaredoxin-1 regulates sirtuin-1 activity through removing glutathione adducts and restores sirtuin-1 activity under oxidative stress. The Bachschmid lab created non-oxidizable mutant sirtuin-1, which retains full activity under oxidative stress. Using gene therapeutic approaches (adeno-associated and adenovirus mediated), over-expression of glutaredoxin-1 or our mutant sirtuin-1 normalized hepatic lipid metabolism and improved plasma dyslipidemia in glutaredoxin-1 knockout mice. We are currently identifying new target proteins of glutaredoxin-1 using omics platforms and systems biology. The lab also screens for small molecules to modify reactive cysteines and prevent protein inactivation by glutathione adducts.


Biochemistry, Pharmacology and Toxicology.

Boston Medical Center




Redox Control of Hepatic Lipid Metabolism
07/01/2015 - 04/30/2020 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK103750-04

Impaired cysteine-thiol redox signaling in metabolic cardiovascular disease
01/01/2016 - 12/31/2018 (PI)
American Heart Association


Regulation of the Cardiac Sodium Channel by SIRTUIN1
06/01/2016 - 05/31/2017 (PI)
The University of Iowa NIH NHLBI
4R01HL115955-04

Regulation of the Cardiac Sodium Channel by SIRTUIN1
08/15/2013 - 05/31/2017 (PI)
The University of Iowa NIH NHLBI
5R01HL115955-03




Yr Title Project-Sub Proj Pubs
2018 Redox control of hepatic lipid metabolism 5R01DK103750-04 5
2017 Redox control of hepatic lipid metabolism 5R01DK103750-03 5
2016 Redox control of hepatic lipid metabolism 5R01DK103750-02 5
2015 Redox control of hepatic lipid metabolism 1R01DK103750-01A1 5
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Taylor E, Huang N, Bodde J, Ellison A, Killiany R, Bachschmid MM, Hamilton J. MRI of atherosclerosis and fatty liver disease in cholesterol fed rabbits. J Transl Med. 2018 Aug 01; 16(1):215.View Related Profiles. PMID: 30068362.
     
  2. Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, van der Velden JLJ, Elko E, Hoffman SM, McMillan DH, Jones JT, Nolin JD, Abdalla S, Schneider R, Seward DJ, Roberson EC, Liptak MD, Cousins ME, Butnor KJ, Taatjes DJ, Budd RC, Irvin CG, Ho YS, Hakem R, Brown KK, Matsui R, Bachschmid MM, Gomez JL, Kaminski N, van der Vliet A, Janssen-Heininger YMW. Reducing protein oxidation reverses lung fibrosis. Nat Med. 2018 Aug; 24(8):1128-1135.View Related Profiles. PMID: 29988126.
     
  3. Luptak I, Sverdlov AL, Panagia M, Qin F, Pimentel DR, Croteau D, Siwik DA, Ingwall JS, Bachschmid MM, Balschi JA, Colucci WS. Decreased ATP production and myocardial contractile reserve in metabolic heart disease. J Mol Cell Cardiol. 2018 Mar; 116:106-114.View Related Profiles. PMID: 29409987; DOI: 10.1016/j.yjmcc.2018.01.017;.
     
  4. Yoon S, Beermann ML, Yu B, Shao D, Bachschmid M, Miller JB. Aberrant Caspase Activation in Laminin-a2-Deficient Human Myogenic Cells is Mediated by p53 and Sirtuin Activity. J Neuromuscul Dis. 2018; 5(1):59-73.View Related Profiles. PMID: 29278895.
     
  5. Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Kietzmann T, Kubaichuk K, Knaus UG, Lopez MG, Olaso-Gonzalez G, Petry A, Schulz R, Vina J, Winyard P, Abbas K, Ademowo OS, Afonso CB, Andreadou I, Antelmann H, Antunes F, Aslan M, Bachschmid MM, Barbosa RM, Belousov V, Berndt C, Bernlohr D, Bertrán E, Bindoli A, Bottari SP, Brito PM, Carrara G, Casas AI, Chatzi A, Chondrogianni N, Conrad M, Cooke MS, Costa JG, Cuadrado A, My-Chan Dang P, De Smet B, Debelec-Butuner B, Dias IHK, Dunn JD, Edson AJ, El Assar M, El-Benna J, Ferdinandy P, Fernandes AS, Fladmark KE, Förstermann U, Giniatullin R, Giricz Z, Görbe A, Griffiths H, Hampl V, Hanf A, Herget J, Hernansanz-Agustín P, Hillion M, Huang J, Ilikay S, Jansen-Dürr P, Jaquet V, Joles JA, Kalyanaraman B, Kaminskyy D, Karbaschi M, Kleanthous M, Klotz LO, Korac B, Korkmaz KS, Koziel R, Kracun D, Krause KH, Kren V, Krieg T, Laranjinha J, Lazou A, Li H, Martínez-Ruiz A, Matsui R, McBean GJ, Meredith SP, Messens J, Miguel V, Mikhed Y, Milisav I, Milkovic L, Miranda-Vizuete A, Mojovic M, Monsalve M, Mouthuy PA, Mulvey J, Münzel T, Muzykantov V, Nguyen ITN, Oelze M, Oliveira NG, Palmeira CM, Papaevgeniou N, Pavicevic A, Pedre B, Peyrot F, Phylactides M, Pircalabioru GG, Pitt AR, Poulsen HE, Prieto I, Rigobello MP, Robledinos-Antón N, Rodríguez-Mañas L, Rolo AP, Rousset F, Ruskovska T, Saraiva N, Sasson S, Schröder K, Semen K, Seredenina T, Shakirzyanova A, Smith GL, Soldati T, Sousa BC, Spickett CM, Stancic A, Stasia MJ, Steinbrenner H, Stepanic V, Steven S, Tokatlidis K, Tuncay E, Turan B, Ursini F, Vacek J, Vajnerova O, Valentová K, Van Breusegem F, Varisli L, Veal EA, Yalçin AS, Yelisyeyeva O, Žarkovic N, Zatloukalová M, Zielonka J, Touyz RM, Papapetropoulos A, Grune T, Lamas S, Schmidt HHHW, Di Lisa F, Daiber A. Corrigendum to "European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]. Redox Biol. 2018 04; 14:694-696. PMID: 29107648.
     
  6. Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Kietzmann T, Kubaichuk K, Knaus UG, Lopez MG, Olaso-Gonzalez G, Petry A, Schulz R, Vina J, Winyard P, Abbas K, Ademowo OS, Afonso CB, Andreadou I, Antelmann H, Antunes F, Aslan M, Bachschmid MM, Barbosa RM, Belousov V, Berndt C, Bernlohr D, Bertrán E, Bindoli A, Bottari SP, Brito PM, Carrara G, Casas AI, Chatzi A, Chondrogianni N, Conrad M, Cooke MS, Costa JG, Cuadrado A, My-Chan Dang P, De Smet B, Debelec-Butuner B, Dias IHK, Dunn JD, Edson AJ, El Assar M, El-Benna J, Ferdinandy P, Fernandes AS, Fladmark KE, Förstermann U, Giniatullin R, Giricz Z, Görbe A, Griffiths H, Hampl V, Hanf A, Herget J, Hernansanz-Agustín P, Hillion M, Huang J, Ilikay S, Jansen-Dürr P, Jaquet V, Joles JA, Kalyanaraman B, Kaminskyy D, Karbaschi M, Kleanthous M, Klotz LO, Korac B, Korkmaz KS, Koziel R, Kracun D, Krause KH, Kren V, Krieg T, Laranjinha J, Lazou A, Li H, Martínez-Ruiz A, Matsui R, McBean GJ, Meredith SP, Messens J, Miguel V, Mikhed Y, Milisav I, Milkovic L, Miranda-Vizuete A, Mojovic M, Monsalve M, Mouthuy PA, Mulvey J, Münzel T, Muzykantov V, Nguyen ITN, Oelze M, Oliveira NG, Palmeira CM, Papaevgeniou N, Pavicevic A, Pedre B, Peyrot F, Phylactides M, Pircalabioru GG, Pitt AR, Poulsen HE, Prieto I, Rigobello MP, Robledinos-Antón N, Rodríguez-Mañas L, Rolo AP, Rousset F, Ruskovska T, Saraiva N, Sasson S, Schröder K, Semen K, Seredenina T, Shakirzyanova A, Smith GL, Soldati T, Sousa BC, Spickett CM, Stancic A, Stasia MJ, Steinbrenner H, Stepanic V, Steven S, Tokatlidis K, Tuncay E, Turan B, Ursini F, Vacek J, Vajnerova O, Valentová K, Van Breusegem F, Varisli L, Veal EA, Yalçin AS, Yelisyeyeva O, Žarkovic N, Zatloukalová M, Zielonka J, Touyz RM, Papapetropoulos A, Grune T, Lamas S, Schmidt HHHW, Di Lisa F, Daiber A. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). Redox Biol. 2017 10; 13:94-162.View Related Profiles. PMID: 28577489.
     
  7. Shao D, Han J, Hou X, Fry J, Behring JB, Seta F, Long MT, Roy HK, Cohen RA, Matsui R, Bachschmid MM. Glutaredoxin-1 Deficiency Causes Fatty Liver and Dyslipidemia by Inhibiting Sirtuin-1. Antioxid Redox Signal. 2017 Aug 20; 27(6):313-327.View Related Profiles. PMID: 27958883; DOI: 10.1089/ars.2016.6716;.
     
  8. Vikram A, Lewarchik CM, Yoon JY, Naqvi A, Kumar S, Morgan GM, Jacobs JS, Li Q, Kim YR, Kassan M, Liu J, Gabani M, Kumar A, Mehdi H, Zhu X, Guan X, Kutschke W, Zhang X, Boudreau RL, Dai S, Matasic DS, Jung SB, Margulies KB, Kumar V, Bachschmid MM, London B, Irani K. Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel. Nat Med. 2017 Mar; 23(3):361-367. PMID: 28191886; DOI: 10.1038/nm.4284;.
     
  9. Kumar S, Kim YR, Vikram A, Naqvi A, Li Q, Kassan M, Kumar V, Bachschmid MM, Jacobs JS, Kumar A, Irani K. Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction. Proc Natl Acad Sci U S A. 2017 02 14; 114(7):1714-1719. PMID: 28137876; DOI: 10.1073/pnas.1614112114;.
     
  10. Han J, Weisbrod RM, Shao D, Watanabe Y, Yin X, Bachschmid MM, Seta F, Janssen-Heininger YMW, Matsui R, Zang M, Hamburg NM, Cohen RA. The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells. Redox Biol. 2016 Oct; 9:306-319.View Related Profiles. PMID: 27693992; DOI: 10.1016/j.redox.2016.09.003;.
     
Showing 10 of 83 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 83 publications over 20 distinct years, with a maximum of 8 publications in 2005

YearPublications
19991
20003
20011
20021
20036
20047
20058
20065
20074
20085
20092
20102
20114
20124
20134
20145
20155
20167
20175
20184
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

cardiovascular
diabetes
glutaredoxin-1
HRas
imaging
metabolism
mitochondria
non-alcoholic fatty liver disease
obesity
oxidative stress
proteomics
sirtuin-1

Dr. Bachschmid has trained multiple graduate and post graduate students in the past. He has vast experience in training students, serving on graduate education programs as faculty including Graduate Medical Sciences and the Molecular and Translational Medicine. Through these programs he has served on several thesis committees. His training style is fostering an open environment and reserve as much time as possible for his trainees. His office door is always open and trainees are welcome to consult him on research or interpersonal problems. He regularly enters the lab to discuss research with his mentees, and will train them in specialized techniques at the bench as needed. He organizes weekly section meeting for the basic research operation of the Vascular Biology Section in which the group discusses laboratory and organizational matters. Every two weeks the section has a journal club, in which trainees present their data or discuss latest publications. For his lab, we have weekly lab meetings (usually 2h duration) to discuss as a group the research progress. He also has weekly individual face-to-face meetings with every trainees to evaluate progress and discuss the next steps and novel ideas.

Available to Mentor as: (Review Mentor Role Definitions):
  • Advisor
  • Career Mentor
  • Project Mentor
  • Research / Scholarly Mentor
Contact for Mentoring:
  • Email (see 'Contact Info')


650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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