Faculty

Robert H Mach, Ph.D.

Britton Chance Professor of Radiology

Department: Radiology

Graduate Group Affiliations

Contact information

Department of Radiology
Vagelos Laboratory, Rm 1012
231 S. 34th Street
Philadelphia, PA 19104

Office: 215-746-8233

Email:
rmach@pennmedicine.upenn.edu

Publications

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Education:
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.

Links
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University of Pennsylvania Faculty Profile

Permanent link

> Perelman School of Medicine > Faculty > Details

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

Gallagher E, Hou C, Zhu Y, Hsieh CJ, Lee H, Li S, Xu K, Henderson P, Chroneos R, Sheldon M, Riley S, Luk KC, Mach RH, McManus MJ.: Positron Emission Tomography with [(18)F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy. Int J Mol Sci 25: 4943, May 2024.

Pees A, Tong J, Birudaraju S, Munot YS, Liang SH, Saturnino Guarino D, Mach RH, Mathis CA, Vasdev N.: Development of Pyridothiophene Compounds for PET Imaging of α-Synuclein. Chemistry 30: e202303921, Apr 2024.

Lee JY, Kim HY, Martorano P, Riad A, Taylor M, Luedtke RR, Mach RH.: In vitro characterization of [(125)I]HY-3-24, a selective ligand for the dopamine D3 receptor. Front Neurosci 18: 1380009, Apr 2024.

Tian GL, Hsieh CJ, Taylor M, Lee JY, Luedtke RR, Mach RH.: Design and Synthesis of D(3)R Bitopic Ligands with Flexible Secondary Binding Fragments: Radioligand Binding and Computational Chemistry Studies. Molecules 29: 123, Dec 2023.

Tian GL, Hsieh CJ, Taylor M, Lee JY, Riad AA, Luedtke RR, Mach RH.: Synthesis of bitopic ligands based on fallypride and evaluation of their affinity and selectivity towards dopamine D(2) and D(3) receptors. Eur J Med Chem 261: 115751, Dec 2023.

Kim HY, Chia WK, Hsieh CJ, Saturnino Guarino D, Graham TJA, Lengyel-Zhand Z, Schneider M, Tomita C, Lougee MG, Kim HJ, Pagar VV, Lee H, Hou C, Garcia BA, Petersson EJ, O'Shea J, Kotzbauer PT, Mathis CA, Lee VM, Luk KC, Mach RH.: A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy. J Med Chem 66: 12185-12202, Sep 2023.

Graham TJA, Lindberg A, Tong J, Stehouwer JS, Vasdev N, Mach RH, Mathis CA.: In Silico Discovery and Subsequent Characterization of Potent 4R-Tauopathy Positron Emission Tomography Radiotracers. J Med Chem 66: 10628-10638, Aug 2023.

Janssen B, Tian G, Lengyel-Zhand Z, Hsieh C-J, Loughee MG, Riad A, Xu K, Hou C, Weng C-C, Lopresti BJ, Kim HJ, Pagar VV, Ferrie JJ, Garcia BA, Mathis CA, Luk K, Petersson EJ, Mach RH: Identification of a putative -synuclein radioligand using an in silico similarity search. Molecular Imaging and Biology 25(4): 704-719, Aug 2023 Notes: DOI: 10.1007/s11307-023-01814-9.

Graham TJA, Lindberg A, Tong J, Stehouwer JS, Vasdev N, Mach RH, Mathis CA: In silico discovery and subsequent characterization of potent 4R-tauopathy Positron Emission Tomography radiotracers. J. Med. Chem Jul 2023 Notes: DOI: 10.1021/acs.jmedchem.3c00775 Online ahead of print.

Han QJ, Forfia P, Vaidya A, Ramani G, deKemp RA, Mach RH, Mankoff DA, Bravo PE, DiCarli M, Chan SY, Waxman AB, Han Y: Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blind, placebo controlled, multicenter study. Front Cardiovasc Med 10: 1118796, Jun 2023 Notes: DOI: 10.3389/fcvm.2023.1118796.