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Robert H Mach, Ph.D.

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Britton Chance Professor of Radiology
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Director, Radiochemistry Research, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
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Department: Radiology
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1f Graduate Group Affiliations 8 a
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Department of Radiology
23 Vagelos Laboratory, Rm 1012
35 231 S. 34th Street
Philadelphia, PA 19104
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2e Office: 215-746-8233
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Email: rmach@pennmedicine.upenn.edu
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18 Publications
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Links
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 8f University of Pennsylvania Faculty Profile
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13 Education:
21 9 B.A. 16 (Chemistry) c
49 State University of New York, College at Potsdam, 1978.
 21 a Ph.D. 1e (Medical Chemistry) c
4d State University of New York at Buffalo, Buffalo, NY, 1985.
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b6 > Perelman School of Medicine   > Faculty   > Details a
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Description of Research Expertise

d1 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.
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60 Keywords. Dopamine D3 receptors, alpha synuclein, PARP-1, neurodegeneration, addiction.
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227 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.
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124 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.
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bd 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.
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Selected Publications

1f7 Stehouwer JS, Huang G, Saturnino Guarino D, Debnath ML, Polu A, Geib SJ, Lopresti B, Ikonomovic MD, Mason N, Mach RH, Mathis CA: Structure-Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1 H-indoles as Tauopathy Positron Emission Tomography Radiotracers. Journal of Medicinal Chemistry. ACS, Vol 68/Issue 6: 6462-6492, Mar 2025 Notes: J Med Chem. 2025 Mar 27;68(6):6462-6492. doi: 10.1021/acs.jmedchem.4c02988. Epub 2025 Mar 11. 58 PMID: 40068019 PMCID: PMC11956013 DOI: 10.1021/acs.jmedchem.4c02988.

 132 Dubroff JG, Hsieh CJ, Wiers CE, Lee H, Li EJ, Schubert EK, Mach RH, Kranzler HR: [11C]Carfentanil PET Whole-Body Imaging of Mu-Opioid Receptors: A First In-Human Study. J. Nucl. Med. J. Nucl. Med, 66(1112-1118): 1112-1118, July 2025.

 145 Hsieh C-J, Saturnino Guarino D, Young AJ, Siderowf AD, Nasrallah I, Schmitz A, Garcia C, Kim HY, Schubert EK, Lee H, Perlmutter JS, Mach RH: Pilot Study of [11C]HY-2-15: A Mixed Alpha-Synuclein and Tau PET Radiotracer. Cells. MDPI, 14(1157), July 2025.

 1e7 Zhao H, Huang T, Dhavale DD, O’Shea JY, Lengyel-Zhand Z, Saturnino Guarino D, Gu J, Yue X, Nai Y-H, Jiang H, Lougee MG, Pagar VV, Kim HJ, Garcia BA, Petersson EJ, Mathis CA, Kotzbauer P, Perlmutter JS, Mach RH, Tu Z: Discovery of N-(6-Methoxypyridin-3-yl)quinoline-2-amine Derivatives for Imaging Aggregated α-Synuclein in Parkinson's Disease with Positron Emission Tomography. Cells. MDPI, 14(1108), July 2025.

 150 Burström V, Xu K, Garro-Martínez E, Mach RH, Sahlholm K, Nibal Betari N: A Nanoluciferase Complementation-based Assay for Monitoring β-arrestin2 Recruitment to the Dopamine D3 Receptor. Biochemistry and Biophysics Reports. Elsevier B.V. 42(102019), April 2025.

 1c5 Tian GL, Hsieh CJ, Guarino DS, Graham TJA, Lengyel-Zhand Z, Schmitz A, Chia WK, Young AJ, Crosby JG, Plakas K, Huang T, Jiang H, Yu Y, Hou C, Lee H, Petersson EJ, Giannakoulias S, O'Shea J, Kotzbauer P, Tu Z, Mathis CA, Mach RH: The Development of a PET Radiotracer for Imaging Alpha Synuclein Aggregates in Parkinson’s Disease. RSC Med Chem RSC Med Chem 10(1039), April 2025.

 12e Li S, Schmitz A, Lu YT, Pal R, Sarkar S, Sellmyer MA, Mach RH, Lee H: Evaluation of a Simplified Radiolabeling Method for a PARP Inhibitor in an Animal Model of Breast Cancer. EJNMMI Research Springer Nature, 15(50), April 2025.

 18f Stehouwer JS, Huang G, Saturnino Guarino D, Debnath ML, Polu A, Geib SJ, Lopresti B, Ikonomovic MD, Mason N, Mach RH, Mathis CA: Structure-Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1 H-indoles as Tauopathy Positron Emission Tomography Radiotracers. J Med. Chem. J Med. Chem, 68(6462-6492), March 2025.

 165 Plakas K, Hsieh CJ, Guarino DS, Hou C, Chia WK, Young A, Schmitz A, Ho YP, Weng CC, Lee H, Li S, Graham TJA, Mach RH: Toward a Small Molecule Antagonist Radioligand for Positron Emission Tomography Imaging of the Mu Opioid Receptor. ACS Chem. Neurosci. ACS, 16(1592-1603), March 2025.

 18a Blizard GS, Dwivedi G, Pan YG, Hou C, Etersque JM, Said H, Chevrier A, Lavertu M, Ni H, Davis B, Tam Y, Cao Q, Mach RH, Weissman D, Alameh MG, Sellmyer MA.: Monitoring mRNA vaccine antigen expression in vivo using PET/CT. Nature Communications 16(1):2234, Mar 2025 Notes: Nat Commun. 2025 Mar 6;16(1):2234. doi: 10.1038/s41467-025-57446-w. 24 PMID: 40044669 PMCID: PMC11882883 14

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