Matthew Springer, PhD

Professor
Medicine
+1 415 502-8404

RESEARCH INTERESTS:

Dr. Matthew L. Springer received his BA from the University of California, Berkeley in 1985 and his PhD from Stanford University in 1992. He did postdoctoral research at Stanford and continued his research there as a senior scientist until joining the UCSF faculty in 2003, where he is currently one of two non-clinicians on the faculty of the Division of Cardiology. The close juxtaposition of his basic research background with the clinical cardiologists in the Division has resulted in an active translational research program.

Dr. Springer's research interests include cell therapy and gene therapy approaches to studying cardiovascular disease, with the goals of exploring potential treatments and understanding underlying mechanisms involved in angiogenesis, vascular function, and treatments for myocardial infarction. The laboratory is studying the therapeutic effects of ultrasound-guided bone marrow cell implantation into the heart after myocardial infarction, with a special emphasis on the therapeutic implications of the age and cardiac disease state of the cell donor. Similarly, the lab is studying the effects of age and disease on circulating angiogenic cells (sometimes called endothelial progenitor cells), with a focus on the roles of endothelial nitric oxide synthase and nitric oxide in the function of these cells. The main angiogenesis interest is how cardiac motion and cyclical forces influences angiogenic gene expression and cell behavior. Currently, a large effort involves the study of vascular reactivity using a rat model of endothelium-dependent flow-mediated vasodilation that they developed, and how vascular endothelial function is affected by exposure to secondhand smoke from tobacco and marijuana.

Publications: 

Abstract 224: Sub-cytotoxic Levels of Heavy Metals Induce Pro-inflammatory Signaling in the Aortic Endothelium without Impairing Flow-Mediated Dilation in Rats.

Circulation research

Pooneh Nabavizadeh, Sharina Ibrahim, Adam Fries, Jiangtao Liu, Ronak Derakhshandeh, Matthew L Springer

Modeling Cardiovascular Risks of E-Cigarettes With Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells.

Journal of the American College of Cardiology

Lee WH, Ong SG, Zhou Y, Tian L, Bae HR, Baker N, Whitlatch A, Mohammadi L, Guo H, Nadeau KC, Springer ML, Schick SF, Bhatnagar A, Wu JC

Vascular endothelial function is impaired by aerosol from a single IQOS HeatStick to the same extent as by cigarette smoke.

Tobacco control

Nabavizadeh P, Liu J, Havel CM, Ibrahim S, Derakhshandeh R, Jacob Iii P, Springer ML

Age-Related Impaired Efficacy of Bone Marrow Cell Therapy for Myocardial Infarction Reflects a Decrease in B Lymphocytes.

Molecular therapy : the journal of the American Society of Gene Therapy

An S, Wang X, Ruck MA, Rodriguez HJ, Kostyushev DS, Varga M, Luu E, Derakhshandeh R, Suchkov SV, Kogan SC, Hermiston ML, Springer ML

Cigarette smoke exposure worsens acute lung injury in antibiotic-treated bacterial pneumonia in mice.

American journal of physiology. Lung cellular and molecular physiology

Gotts JE, Chun LF, Abbott J, Fang X, Takasaki N, Nishimura SL, Springer ML, Schick SF, Calfee CS, Matthay MA

Marijuana, Secondhand Smoke, and Social Acceptability.

JAMA internal medicine

Glantz SA, Halpern-Felsher B, Springer ML

One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function.

Journal of the American Heart Association

Wang X, Derakhshandeh R, Liu J, Narayan S, Nabavizadeh P, Le S, Danforth OM, Pinnamaneni K, Rodriguez HJ, Luu E, Sievers RE, Schick SF, Glantz SA, Springer ML

San Francisco Medicine

CANNABIS: Clearing some smoke?

Springer ML

Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.

Psychoneuroendocrinology

Aschbacher K, Derakhshandeh R, Flores AJ, Narayan S, Mendes WB, Springer ML

Overexpression of Nitric Oxide Synthase Restores Circulating Angiogenic Cell Function in Patients With Coronary Artery Disease: Implications for Autologous Cell Therapy for Myocardial Infarction.

Journal of the American Heart Association

Chen Q, Varga M, Wang X, Haddad DJ, An S, Medzikovic L, Derakhshandeh R, Kostyushev DS, Zhang Y, Clifford BT, Luu E, Danforth OM, Rafikov R, Gong W, Black SM, Suchkov SV, Fineman JR, Heiss C, Aschbacher K, Yeghiazarians Y, Springer ML

Impairment of Endothelial Function by Little Cigar Secondhand Smoke.

Tobacco regulatory science

Liu J, Wang X, Narayan S, Glantz SA, Schick SF, Springer ML

Protein engineering to develop a redox insensitive endothelial nitric oxide synthase

Redox Biol

Rafikov R, Kumar S, Aggarwal S, Pardo D, Fonseca FV, Ransom J, Rafikova O, Chen Q, Springer ML, Black SM

Brief exposure to secondhand smoke reversibly impairs endothelial vasodilatory function.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

Pinnamaneni K, Sievers RE, Sharma R, Selchau AM, Gutierrez G, Nordsieck EJ, Su R, An S, Chen Q, Wang X, Derakhshandeh R, Aschbacher K, Heiss C, Glantz SA, Schick SF, Springer ML

Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients.

The British journal of nutrition

Horn P, Amabile N, Angeli FS, Sansone R, Stegemann B, Kelm M, Springer ML, Yeghiazarians Y, Schroeter H, Heiss C

Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.

PloS one

Fang Q, Mok PY, Thomas AE, Haddad DJ, Saini SA, Clifford BT, Kapasi NK, Danforth OM, Usui M, Ye W, Luu E, Sharma R, Bartel MJ, Pathmanabhan JA, Ang AA, Sievers RE, Lee RJ, Springer ML

Pharmacological inhibition of S-nitrosoglutathione reductase improves endothelial vasodilatory function in rats in vivo.

Journal of applied physiology (Bethesda, Md. : 1985)

Chen Q, Sievers RE, Varga M, Kharait S, Haddad DJ, Patton AK, Delany CS, Mutka SC, Blonder JP, Dubé GP, Rosenthal GJ, Springer ML

Gene therapy and angiogenesis

Cardiology: An Illustrated Textbook. K. Chatterjee et al., eds.

Springer ML

Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair.

Science translational medicine

Lin YD, Luo CY, Hu YN, Yeh ML, Hsueh YC, Chang MY, Tsai DC, Wang JN, Tang MJ, Wei EI, Springer ML, Hsieh PC

Advanced Donor Age Impairs Bone Marrow Cell Therapeutic Efficacy for Cardiac Disease.

Journal of tissue science & engineering

Wang X, Takagawa J, Haddad DJ, Pinnamaneni K, Zhang Y, Sievers RE, Grossman W, Yeghiazarians Y, Springer ML

Higher fasting glucose levels are associated with reduced circulating angiogenic cell migratory capacity among healthy individuals.

American journal of cardiovascular disease

Aschbacher K, Chen Q, Varga M, Haddad DJ, Yeghiazarians Y, Epel E, Wolkowitz OM, Springer ML

Donor myocardial infarction impairs the therapeutic potential of bone marrow cells by an interleukin-1-mediated inflammatory response.

Science translational medicine

Wang X, Takagawa J, Lam VC, Haddad DJ, Tobler DL, Mok PY, Zhang Y, Clifford BT, Pinnamaneni K, Saini SA, Su R, Bartel MJ, Sievers RE, Carbone L, Kogan S, Yeghiazarians Y, Hermiston M, Springer ML

The launch of American Journal of Cardiovascular Disease

Am J Cardiovasc Dis

Roberts WC, Springer ML, Wang X, Wang D

Timing of bone marrow cell therapy is more important than repeated injections after myocardial infarction

Cardiovasc Pathol

Zhang Y, Sievers RE, Prasad M, Mirsky R, Shih H, Wong ML, Angeli FS, Ye J, Takagawa J, Koskenvuo JW, Springer ML, Grossman W, Boyle AJ, Yeghiazarians Y

Nitric oxide synthase expression and functional response to nitric oxide are both important modulators of circulating angiogenic cell response to angiogenic stimuli.

Arteriosclerosis, thrombosis, and vascular biology

Heiss C, Schanz A, Amabile N, Jahn S, Chen Q, Wong ML, Rassaf T, Heinen Y, Cortese-Krott M, Grossman W, Yeghiazarians Y, Springer ML

Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease.

Journal of the American College of Cardiology

Heiss C, Jahn S, Taylor M, Real WM, Angeli FS, Wong ML, Amabile N, Prasad M, Rassaf T, Ottaviani JI, Mihardja S, Keen CL, Springer ML, Boyle A, Grossman W, Glantz SA, Schroeter H, Yeghiazarians Y

Assessment of myocardial angiogenesis and vascularity in small animal models.

Methods in molecular biology (Clifton, N.J.)

Springer ML

Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy.

Molecular therapy : the journal of the American Society of Gene Therapy

Yeghiazarians Y, Zhang Y, Prasad M, Shih H, Saini SA, Takagawa J, Sievers RE, Wong ML, Kapasi NK, Mirsky R, Koskenvuo J, Minasi P, Ye J, Viswanathan MN, Angeli FS, Boyle AJ, Springer ML, Grossman W

Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium.

Arteriosclerosis, thrombosis, and vascular biology

Li X, Tjwa M, Van Hove I, Enholm B, Neven E, Paavonen K, Jeltsch M, Juan TD, Sievers RE, Chorianopoulos E, Wada H, Vanwildemeersch M, Noel A, Foidart JM, Springer ML, von Degenfeld G, Dewerchin M, Blau HM, Alitalo K, Eriksson U, Carmeliet P, Moons L

Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production.

Journal of the American College of Cardiology

Heiss C, Amabile N, Lee AC, Real WM, Schick SF, Lao D, Wong ML, Jahn S, Angeli FS, Minasi P, Springer ML, Hammond SK, Glantz SA, Grossman W, Balmes JR, Yeghiazarians Y

Pleiotrophin induces nitric oxide dependent migration of endothelial progenitor cells.

Journal of cellular physiology

Heiss C, Wong ML, Block VI, Lao D, Real WM, Yeghiazarians Y, Lee RJ, Springer ML

In vivo measurement of flow-mediated vasodilation in living rats using high-resolution ultrasound.

American journal of physiology. Heart and circulatory physiology

Heiss C, Sievers RE, Amabile N, Momma TY, Chen Q, Natarajan S, Yeghiazarians Y, Springer ML

Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approaches.

Journal of applied physiology (Bethesda, Md. : 1985)

Takagawa J, Zhang Y, Wong ML, Sievers RE, Kapasi NK, Wang Y, Yeghiazarians Y, Lee RJ, Grossman W, Springer ML

Localization of vascular response to VEGF is not dependent on heparin binding.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Springer ML, Banfi A, Ye J, von Degenfeld G, Kraft PE, Saini SA, Kapasi NK, Blau HM

355: Increased circulating endothelial microparticles predict hemodynamic severity of untreated pulmonary hypertension.

The Journal of Heart and Lung Transplantation

N. Amabile, C. Heiss, W.M. Real, P. Minasi, M.L. Springer, D. McGoughlin, E.J. Rame, W. Grossman, T. de Marco, Y. Yeghiazarians

356: Reduced number and function of circulating endothelial progenitor cells in patients with pulmonary arterial hypertension.

The Journal of Heart and Lung Transplantation

R.K. Rao, J. Ye, W.M. Real, M. Springer, W. Grossman, T. de Marco, Y. Yeghiazarians

Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction.

American journal of physiology. Heart and circulatory physiology

Zhang Y, Takagawa J, Sievers RE, Khan MF, Viswanathan MN, Springer ML, Foster E, Yeghiazarians Y

A balancing act: therapeutic approaches for the modulation of angiogenesis.

Current opinion in investigational drugs (London, England : 2000)

Springer ML

239. Histological Measurement of Myocardial Infarct Area Does Not Provide a Sensitive Assessment of Infarct Size in a Mouse Chronic Infarct Model.

Molecular Therapy

Junya Takagawa, Yan Zhang, Richard E. Sievers, Neel K. Kapasi, Maelene L. Wong, Yerem Yeghiazarians, Randall J. Lee, William Grossman, Matthew L. Springer

453. Injectionof Different Adult Cell Types into Mouse Myocardium Three Days after Myocardial Infarction Using a Novel Echo-Guided Technique Improves Cardiac Function.

Molecular Therapy

Yan Zhang, Junya Takagawa, Richard E. Sievers, Maelene L. Wong, Christian Heiss, Mohan N. Viswanathan, Neel K. Kapasi, Jianqin Ye, Elyse Foster, William Grossman, Matthew L. Springer, Yerem Yeghiazarians

Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia

FASEBJ

von Degenfeld G, Banfi A, Springer ML, Wagner RA, Jacobi J, Ozawa CR, Merchant MJ, Cooke JP, Blau HM

VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature.

American journal of physiology. Heart and circulatory physiology

Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, Norberg SM, O'Brien SM, Davis RB, Gowen LC, Anderson KD, Thurston G, Joho S, Springer ML, Kuo CJ, McDonald DM

Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography.

American journal of physiology. Heart and circulatory physiology

Springer ML, Sievers RE, Viswanathan MN, Yee MS, Foster E, Grossman W, Yeghiazarians Y

Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis.

The Journal of clinical investigation

Ozawa CR, Banfi A, Glazer NL, Thurston G, Springer ML, Kraft PE, McDonald DM, Blau HM

Myoblast-mediated gene transfer for therapeutic angiogenesis and arteriogenesis.

British journal of pharmacology

von Degenfeld G, Banfi A, Springer ML, Blau HM

Localized arteriole formation directly adjacent to the site of VEGF-induced angiogenesis in muscle.

Molecular therapy : the journal of the American Society of Gene Therapy

Springer ML, Ozawa CR, Banfi A, Kraft PE, Ip TK, Brazelton TR, Blau HM

RIP2, a checkpoint in myogenic differentiation.

Molecular and cellular biology

Munz B, Hildt E, Springer ML, Blau HM

Gene delivery to muscle.

Current protocols in human genetics

Springer ML, Rando TA, Blau HM

Myoblast-mediated gene transfer for therapeutic angiogenesis.

Methods in enzymology

Banfi A, Springer ML, Blau HM

Not the usual suspects: the unexpected sources of tissue regeneration.

The Journal of clinical investigation

Springer ML, Brazelton TR, Blau HM

VEGF gene delivery to myocardium: deleterious effects of unregulated expression.

Circulation

Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM

Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factor.

The journal of gene medicine

Springer ML, Hortelano G, Bouley DM, Wong J, Kraft PE, Blau HM

A novel means of drug delivery: myoblast-mediated gene therapy and regulatable retroviral vectors.

Annual review of pharmacology and toxicology

Ozawa CR, Springer ML, Blau HM

Angiogenesis monitored by perfusion with a space-filling microbead suspension.

Molecular therapy : the journal of the American Society of Gene Therapy

Springer ML, Ip TK, Blau HM

Ex vivo gene therapy using myoblasts and regulatable retroviral vectors

In Gene Therapy: Therapeutic Mechanisms and Strategies, NS Templeton and DD Lasic, eds.

Ozawa CR, Springer ML, Blau HM

Analysis of immune responses to varicella zoster viral proteins induced by DNA vaccination.

Antiviral research

Abendroth A, Slobedman B, Springer ML, Blau HM, Arvin AM

VEGF gene delivery to muscle: potential role for vasculogenesis in adults.

Molecular cell

Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM

Inhibition of solid tumor growth by Fas ligand-expressing myoblasts.

Somatic cell and molecular genetics

Springer ML, Kraft PE, Blau HM

Immune response and myoblasts that express Fas ligand.

Science (New York, N.Y.)

Kang SM, Hoffmann A, Le D, Springer ML, Stock PG, Blau HM

High-efficiency retroviral infection of primary myoblasts.

Somatic cell and molecular genetics

Springer ML, Blau HM

Towards a treatment for Tay-Sachs disease

Molec. Med. Today

Springer, ML

Muscle-mediated gene therapy.

The New England journal of medicine

Blau HM, Springer ML

Gene therapy--a novel form of drug delivery.

The New England journal of medicine

Blau HM, Springer ML

Cell implantation treatment for MPS VII

Molec. Med. Today

Springer, ML

Stage-specific requirement for myosin II during Dictyostelium development.

Development (Cambridge, England)

Springer ML, Patterson B, Spudich JA

Genetic control of fungal differentiation: the three sporulation pathways of Neurospora crassa.

BioEssays : news and reviews in molecular, cellular and developmental biology

Springer ML

Timing of synthesis and cellular localization of two conidiation-specific proteins of Neurospora crassa.

Developmental biology

Springer ML, Hager KM, Garrett-Engele C, Yanofsky C