David S. Goldstein, M.D., Ph.D.

Headshot of David S. Goldstein
Senior Investigator
Autonomic Medicine Section

BG 10 RM 8N260

Dr. Goldstein graduated from Yale College and received an M.D.-Ph.D. in Behavioral Sciences from Johns Hopkins. After medical internship and residency at the University of Washington, he came to the NIH as a Clinical Associate in the NHLBI, obtaining tenure as a Senior Investigator in 1984. He joined the NINDS in 1990 to head the Clinical Neurochemistry Section and founded the Clinical Neurocardiology Section (name changed to Autonomic Medicine Section in 2019). He has received Yale's Angier Prize for Research in Psychology, the Laufberger Medal of the Czech Academy of Sciences, 2 NIH Merit Awards, the Founders Award of the Bakken Heart-Brain Institute, the Distinguished Investigator Award of the Society for Clinical and Translational Science, and the NIH Distinguished Clinical Teacher Award. Additionally, Dr. Goldstein also directs the UCNS-accredited Clinical Fellowship in Autonomic Disorders at the NIH Clinical Center. 

Additionally, Dr. Goldstein, is author of more than 600 research articles and several books, including "Adrenaline and the Inner World: An Introduction to Scientific Integrative Medicine," ”Dysautonomias: A Handbook for Patients,” "Stress, Catecholamines, and Cardiovascular Disease," "The Autonomic Nervous System in Health and Disease,” and the e-book, "Principles of Autonomic Medicine." He also directs the UCNS-accredited Clinical Fellowship in Autonomic Disorders at the NIH Clinical Center.

Research of the Autonomic Medicine Section (AMS) focuses on autonomic and catecholamine-related disorders, using a mainly patient-oriented approach. In the prospective longitudinal PDRisk study (NIH Clinical Protocol 09N0010) we are assessing whether in individuals who have multiple risk factors for Parkinson disease (PD) biomarkers of central or cardiac catecholamine deficiency predict the development of PD during up to 7.5 years of follow-up. As part of NIH Clinical Protocol 18N0140, “Clinical Laboratory Evaluation of Chronic Autonomic Failure,” we are conducting a prospective natural history study to test the hypothesis that Lewy body neurogenic orthostatic hypotension (nOH) without signs of central neurodegeneration may evolve into PD+nOH or dementia with Lewy bodies+nOH. In this protocol we are also combining clinical catecholamine neurochemistry, 18F-dopamine sympathetic neuroimaging, and quantitative immunofluorescence microscopy to distinguish among chronic autonomic failure syndromes.

In a collaborative genotype-phenotype study of alpha-synuclein/tyrosine hydroxylase colocalization in skin biopsies we are identifying which forms of familial PD are associated with peripheral intra-neuronal synucleinopathy. We are using a computational modeling approach based on homeostasis and the catecholaldehyde hypothesis for the pathogenesis of PD to predict the progression of catecholaminergic neurodegeneration in Lewy body diseases. We are applying cerebrospinal fluid catecholamine neurochemistry and multi-tracer central and peripheral neuroimaging to identify dysfunctional but extant catecholaminergic neurons—the “sick-but-not-dead” phenomenon. We are collaborating in a clinical trial of type 2 adeno-associated virus-glial cell line-derived neurotrophic factor to treat multiple system atrophy.

Clinical Protocol:

1.  Goldstein DS (2022)

Principles of Autonomic Medicine (Export to ZIP file)

2.  Goldstein DS (2019)

How does homeostasis happen? Integrative physiologic, systems biologic, and evolutionary perspectives

Am J Physiol (Regul Integr Comp Physiol), 316, R301-R317.(PMID 28918243)

3.  Goldstein DS, Pekker M, Eisenhofer G, Sharabi Y. (2019)

Computational modeling reveals multiple abnormalities of myocardial noradrenergic function in Lewy body diseases

JCI Insight , doi: 10.1172/jci.insight.130441, (PMID 31335324)

4.  Isonaka R, Rosenberg AZ, Sullivan P, Corrales A, Holmes C, Sharabi Y, Goldstein DS (2019)

Alpha-synuclein deposition within sympathetic noradrenergic neurons is associated with myocardial noradrenergic deficiency in neurogenic orthostatic hypotension.

Hypertension 73, 910-918. (PMID 30798661)

5.  Goldstein DS, Sullivan P, Holmes C, Mash DC, Kopin IJ, Sharabi Y (2017)

Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy.

Park Rel Dis 35, 88-91. (PMID 28034624)

6.  Goldstein DS, Holmes C, Sharabi Y, Wu T (2015)

Survival in synucleinopathies: A prospective cohort study.

Neurology 85, 1554-1561. (PMID 26432848)

7.  Goldstein DS. (2013)

Concepts of scientific integrative medicine applied to the physiology and pathophysiology of catecholamine systems.

Compr Physiol, 3, 1569-1610. (PMID 24265239).

8.  Goldstein DS, Sullivan P, Holmes C, Miller GW, Alter S, Strong G, Mash DC, Kopin IJ, Sharabi Y. (2013)

Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson disease.

J Neurochem, 123, 591-603. (PMID: 23786406).

9.  Goldstein DS. (2006)

Adrenaline and the Inner World: An Introduction to Scientific Integrative Medicine

Johns Hopkins University Press

10. Eisenhofer G, Kopin IJ, Goldstein DS. (2004)

Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine

Pharmacol Rev, 56, 331-349

11. Goldstein DS, Eisenhofer G, Kopin IJ. (2003)

Sources and significance of plasma levels of catechols and their metabolites in humans

J Pharmacol Exp Ther, 305, 800-811

12. Goldstein DS, Katzper M, Linares O, Kopin IJ (2002)

Kinetic model for the fate of the sympathoneural imaging agent 6-[18F]fluorodopamine in the human heart: A novel means to assess cardiac sympathetic neuronal function.

Naunyn-Schmiedeberg’s Arch Pharmacol 365, 38-49 (PMID 11862332)

13. Goldstein DS (2001)

The Autonomic Nervous System in Health and Disease

Taylor & Francis

14. Goldstein DS, Holmes C, Li S-T, Bruce S, Metman LV, Cannon RO III (2000)

Cardiac sympathetic denervation in Parkinson disease.

Ann Intern Med 133, 338-347. (PMID 10979878)

15. Goldstein DS, Holmes C, Cannon RO III, Eisenhofer G, Kopin IJ (1997)

Sympathetic cardioneuropathy in dysautonomias

N Engl J Med, 336, 696-702

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