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

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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

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. PMID: 40068019 PMCID: PMC11956013 DOI: 10.1021/acs.jmedchem.4c02988.

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 Communication 16(1):2234, Mar 2025 Notes: Nat Commun. 2025 Mar 6;16(1):2234. doi: 10.1038/s41467-025-57446-w. PMID: 40044669 PMCID: PMC11882883

Shihong Li, Alexander Schmitz, Yu-Ting Lu, Rammyani Pal, Swarbhanu Sarkar, Mark A. Sellmyer, Robert H. Mach, Hsiaoju Lee: Automation of simplified two-step radiolabeling via ditosylate synthon for 18F-labeled radiotracers using AllinOne module. Nucl Med Biol February 2025 Notes: 138-139: 108948. doi:10.1016/j.nucmedbio.2024.108948 PMID: 39277961 PMCID: PMC11714026 DOI: 10.1016/j.nucmedbio.2024.108948.

McDonald ES, Pan TC, Pant DK, Troester MA, Kossenkov AV, Mankoff DA, Mach RH, Chodosh LA.: Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence. Cancer Research Communications. AACR Journals, 5(2):226-239: 226–239, Feb 2025 Notes: Cancer Res Commun. 2025 Feb 1;5(2):226-239. doi: 10.1158/2767-9764.CRC-23-0562. PMID: 39804138 PMID: 39804138 PMCID: PMC11791746 DOI: 10.1158/2767-9764.CRC-23-0562 Cancer Research Communications (2025) 5 (2): 226–239.

Weeks JK, Pantel AR, Gitto SB, Liu F, Schubert EK, Pryma DA, Farwell MD, Mankoff DA, Mach RH, Simpkins F, Lin LL.: [18F]Fluorthanatrace PET in Ovarian Cancer: Comparison with [18F]FDG PET, Lesion Location, Tumor Grade, and Breast Cancer Gene Mutation Status. Journal of Nuclear Medicine 66(1):34-39: 34-39, Jan 2025 Notes: J Nucl Med. 2025 Jan 3;66(1):34-39. doi: 10.2967/jnumed.124.267627. PMID: 39638432 Journal of Nuclear Medicine January 2025, 66 (1) 34-39; DOI: https://doi.org/10.2967/jnumed.124.267627.

Saturnino Guarino D, Miranda Azpiazu P, Sunnemark D, Elmore CS, Bergare J, Artelsmair M, Nordvall G, Forsberg Morén A, Jia Z, Cortes-Gonzalez M, Mach RH, Wilcox KC, Finnema S, Schou M, Varrone A.: Identification and In Vitro and In Vivo Characterization of KAC-50.1 as a Potential α-Synuclein PET Radioligand. ACS Chem Neurosci. ACS, 15(22):4210-4219: 4210-4219, Nov 2024 Notes: ACS Chem Neurosci. 2024 Nov 20;15(22):4210-4219. doi:10.1021/acschemneuro.4c00493. PMID: 39528351 PMCID: PMC11587505 DOI: 10.1021/acschemneuro.4c00493.

Young AJ, Pantel AR, Kiani M, Doot RK, Bagheri S, Pryma DA, Farwell MD, Li S, Lee H, Schubert EK, Secreto A, Zuckerman SP, Nayak A, Choi H, Carlin S, DeMichele A, Mankoff DA, Zhou R, Mach RH, McDonald ES.: Kinetic Analysis and Metabolism of Poly(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET in Breast Cancer. J Nucl Med Dec 2024 Notes: J Nucl Med. 2024 Dec 3;65(12):1862-1868. doi: 10.2967/jnumed.124.268254. PMID: 39477499 PMCID: PMC11619586 DOI: 10.2967/jnumed.124.268254.

Alameh MG, Semon A, Bayard NU, Pan YG, Dwivedi G, Knox J, Glover RC, Rangel PC, Tanes C, Bittinger K, She Q, Hu H, Bonam SR, Maslanka JR, Planet PJ, Moustafa AM, Davis B, Chevrier A, Beattie M, Ni H, Blizard G, Furth EE, Mach RH, Lavertu M, Sellmyer MA, Tam Y, Abt MC, Weissman D, Zackular JP.: A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection. Science. 2024 Oct 3;386(6717):69–75: 69–75, Oct 2024 Notes: Science. 2024 Oct 3;386(6717):69–75. doi: 10.1126/science.adn4955 Science. 2024 Oct 4;386(6717):69-75. doi: 10.1126/science.adn4955. Epub 2024 Oct 3. PMID: 39361752 PMCID: PMC11719173 DOI: 10.1126/science.adn4955.

Zhu Y, Kohli N, Young A, Sheldon M, Coni J, Rajasekaran M, Robinson L, Chroneos R, Riley S, Guarnieri JW, Jose J, Patel N, Wallace DC, Li S, Lee H, Mach RH, McManus MJ.: PET Imaging with [18F]ROStrace Detects Oxidative Stress and Predicts Parkinson's Disease Progression in Mice. Antioxidants. MDPI, 13(10):1226, Oct 2024 Notes: Antioxidants (Basel). 2024 Oct 12;13(10):1226. doi: 10.3390/antiox13101226. PMID: 39456479 PMCID: PMC11504722 DOI: 10.3390/antiox13101226.

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.