Robert H Mach, Ph.D.

faculty photo
Britton Chance Professor of Radiology
Department: Radiology
Graduate Group Affiliations

Contact information
Department of Radiology
Vagelos Laboratory, Rm 1010
231 S. 34th Street
Philadelphia, PA 19104
Office: 215-746-8233
B.A. (Chemistry)
State University of New York, College at Potsdam, 1978.
Ph.D. (Medical Chemistry)
State University of New York at Buffalo, Buffalo, NY, 1985.
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Description of Research Expertise

Research Interests. Research in my lab is focused on development of radiotracers for studying the molecular basis of disease using the imaging technique, positron emission tomography or PET.

Keywords. Dopamine D3 receptors, alpha synuclein, PARP-1, neurodegeneration, addiction.

Research Details. My current research projects include the development of radiotracers for imaging: 1) dopamine D3 receptors in addiction; 2) alpha synuclein in Parkinson’s disease and other synucleinopathies; and 3) PARP-1 in cancer and CNS disorders. My laboratory is also studying cancer cell biology, and identified the role of a ternary complex between the sigma-2 receptor/TMEM97, LDL receptor, and progesterone receptor membrane component 1 (PGRMC1) in providing the high levels of cholesterol needed to support cell proliferation.

Rotation Projects. 1) In silico and computational chemistry methods for identifying small molecule - protein interactions. 2) Mechanism of receptor mediated internalization mediated by the TMEM97-sigma-2 receptor/PGRMC1 protein complex. 3) Molecular imaging of CNS receptors with PET.

Lab Personnel. The Mach lab currently has 1 graduate student, 3 postdoctoral research associates in cell biology, 3 postdoctoral research associates in chemistry and 5 support staff.

Selected Publications

Xu K, Hsieh CJ, Lee JY, Riad A, Izzo NJ, Look G, Catalano S, Mach RH.: Exploration of Diazaspiro Cores as Piperazine Bioisosteres in the Development of σ2 Receptor Ligands. Int J Mol Sci 23: 8259, Jul 2022.

Hsieh CJ, Hou C, Zhu Y, Lee JY, Kohli N, Gallagher E, Xu K, Lee H, Li S, McManus MJ, Mach RH.: [(18)F]ROStrace detects oxidative stress in vivo and predicts progression of Alzheimer's disease pathology in APP/PS1 mice. EJNMMI Res 12: 43, Jul 2022.

Kim HY, Lee JY, Hsieh CJ, Riad A, Izzo NJ, Catalano SM, Graham TJA, Mach RH.: Screening of σ(2) Receptor Ligands and In Vivo Evaluation of (11)C-Labeled 6,7-Dimethoxy-2-[4-(4-methoxyphenyl)butan-2-yl]-1,2,3,4-tetrahydroisoquinoline for Potential Use as a σ(2) Receptor Brain PET Tracer. J Med Chem 65: 6261-6272, Apr 2022.

Lee HS, Schwarz SW, Schubert EK, Chen DL, Doot RK, Makvandi M, Lin LL, McDonald ES, Mankoff DA, Mach RH.: The Development of (18)F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1. Radiol Imaging Cancer 2022.

Lengyel-Zhand Z, Puentes LN, Mach RH.: PARkinson's: From cellular mechanisms to potential therapeutics. Pharmacol Ther 2022.

Young AJ, Pantel AR, Viswanath V, Dominguez TL, Makvandi M, Lee H, Li S, Schubert EK, Pryma DA, Farwell MD, Mach RH, Simpkins F, Lin LL, Mankoff DA, Doot RK.: Kinetic and Static Analysis of Poly-(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted (18)F-Fluorthanatrace PET Images of Ovarian Cancer. J Nucl Med 2022.

Puentes LN, Makvandi M, Mach RH.: Molecular Imaging: PARP-1 and Beyond. J Nucl Med 62: 765-770, Jun 2021.

Puentes LN, Lengyel-Zhand Z, Lee JY, Hsieh CJ, Schneider ME Jr, Edwards KJ, Luk KC, Lee VM, Trojanowski JQ, Mach RH.: Poly (ADP-ribose) Interacts With Phosphorylated α-Synuclein in Post Mortem PD Samples. Front Aging Neurosci 13: 704041, Jun 2021.

Lee B, Taylor M, Griffin SA, McInnis T, Sumien N, Mach RH, Luedtke RR.: Evaluation of Substituted N-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands. Molecules 26: 3182, May 2021.

Hsieh CJ, Riad A, Lee JY, Sahlholm K, Xu K, Luedtke RR, Mach RH.: Interaction of Ligands for PET with the Dopamine D3 Receptor: In Silico and In Vitro Methods. Biomolecules 11: 529, Apr 2021.

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Last updated: 08/08/2022
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