About

Donna Huryn is a Professor of Practice in the Department of Chemistry at the University of Pennsylvania. She is based in Chem 73, with her office located in Room 450 and her laboratory in Room 432. Her primary focus area is Organic Chemistry. The information provided on the department's people page highlights her role and contact details but does not include further details about her research background, specific projects, or key contributions.

Research topics

• Biology
• Medicine
• Internal medicine
• Bioinformatics
• Biochemistry
• Organic chemistry
• Biophysics
• Pharmacology
• Crystallography
• Genetics
• Computational biology
• Chemistry

Selected publications

• Nef and Vpu protect infected cells from ADCP mediated by plasma from people with HIV-1

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-15

  article

  ABSTRACT The HIV-1 envelope glycoprotein (Env) represents the only viral antigen at the surface of infected cells, making it an ideal target for antibody-based therapies. Most antibodies elicited in people with HIV (PWH) do not recognize Env in its native “closed” conformation but readily bind to Env when it samples the CD4-bound “open” conformation. Downregulation of CD4 at the surface of infected cells by the viral accessory proteins Nef and Vpu prevents the premature opening of Env and has been shown to protect infected cells from antibody-dependent cellular cytotoxicity (ADCC) mediated by PWH plasma. Here, we report that deletion of Nef and Vpu from primary infectious molecular clones renders infected cells vulnerable to antibody-dependent cellular phagocytosis (ADCP) mediated by PWH plasma. This is in part linked to the premature engagement of Env with CD4. In agreement with an “open” Env being vulnerable to ADCP, small CD4 mimetic compounds (CD4mc) sensitize in vitro -infected cells and ex vivo -expanded CD4 T cells to ADCP mediated by autologous monocytes in presence of PWH plasma. This effect was further improved by increasing cell surface Env through IFN-induced BST-2 upregulation. IMPORTANCE Developing new therapies to eliminate HIV-1-infected cells is essential to decrease the size of the HIV-1 reservoir. Fc-effector functions such as antibody dependent cellular cytotoxicity (ADCC) have shown potential in eliminating in vitro- infected cells and ex vivo- expanded infected cells from people with HIV, decreasing the size of the reservoir and delaying viral rebound in humanized mice. Here, we report that antibody dependent cellular phagocytosis (ADCP) can also be harnessed to eliminate HIV-1-infected cells. We show that infected cells harboring “open” Env conformations are susceptible to ADCP-mediated killing in the presence of plasma from people with HIV. A better understanding of the contribution of different Fc-effector functions in the elimination of infected cells could help guide the development of new therapeutic approaches toward an HIV-1 cure.

  PublisherDOI

• Drug Discovery: Hit and Lead Identification

  Garland Science eBooks · 2025-10-30

  book-chapterSenior author
  PublisherDOI

• Lead Optimization: Properties Optimized and Medicinal Chemistry Strategies

  Garland Science eBooks · 2025-10-30

  book-chapterSenior author
  PublisherDOI

• 2024 VCP International Conference: Exploring multi - disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein , to the therapeutic advancement for VCP - associated multisystem proteinopathy

  2025-02-03

  preprintOpen access

  Valosin-containing protein (VCP/p97) is a ubiquitously expressed AAA+ ATPase associated with numerous protein-protein interactions and critical cellular functions including protein degradation and clearance, mitochondrial homeostasis, DNA repair and replication, cell cycle regulation, endoplasmic reticulum-associated degradation, and lysosomal functions including autophagy and apoptosis. Autosomal-dominant missense mutations in the VCP gene may result in VCP-associated multisystem proteinopathy (VCP-MSP), a rare degenerative disorder linked to heterogeneous phenotypes including inclusion body myopathy (IBM) with Paget’s disease of bone (PDB) and frontotemporal dementia (FTD) or IBMPFD, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), parkinsonism, Charcot-Marie Tooth disease (CMT), and spastic paraplegia. The complexity of VCP-MSP makes collaboration among stakeholders essential and necessitates a multi-disciplinary approach.The 2024 VCP International Conference was hosted at Caltech between February 22 and 25. Co-organized by Cure VCP Disease and Dr. Tsui-Fen Chou, the meeting aimed to center the patient as a research partner, harmonize diverse stakeholder engagement, and bridge the gap between basic and clinical neuroscience as it relates to VCP-MSP. Over 100 multi-disciplinary experts attended, ranging from basic scientists to clinicians to patient advocates. Attendees discussed genetics and clinical presentation, cellular and molecular mechanisms underlying disease, therapeutic approaches, and strategies for future VCP research. The conference included three roundtable discussions, 29 scientific presentations, 32 scientific posters, nine patient and caregiver posters, and a closing discussion forum. The following conference proceedings summarize these sessions, highlighting both the identified gaps in knowledge and the significant strides made towards understanding and treating VCP diseases.

  PublisherDOI

• Antitumor Efficacy of 1,2,4-Triazole-Based VCP/p97 Allosteric Inhibitors

  Journal of Medicinal Chemistry · 2025-07-03 · 4 citations

  articleSenior authorCorresponding

  The AAA ATPase p97 (VCP) plays a crucial role in maintaining protein homeostasis through the ubiquitin-proteosome pathway, as well as other mechanisms. Due to the increased mutational load and protein quality control failures in cancer cells, p97 is a potential target for cancer therapy. Here, we highlight the optimization of the previously reported 3-thioalkyl-1,2,4-triazol-pyridyl allosteric inhibitor scaffold and identify two compounds (25 and 38) with low-nanomolar biochemical potency, submicromolar cellular inhibition, in vivo effects on biomarkers of VCP inhibition, and antitumor efficacy in mouse xenograft tumor models. Furthermore, compound 38 demonstrated robust inhibition of VCP ATP-site mutant proteins and growth of cells resistant to the known ATP-competitive inhibitor CB-5083.

  PublisherDOI

• Medicinal Chemistry

  Garland Science eBooks · 2025-10-30

  bookSenior author

  This book provides a concise introduction to the medicinal chemistry of therapeutically active compounds. Written in an accessible style, it offers a brief overview of the drug development process, from discovery to approved drug. Emphasizing medicinal chemistry strategies, the content is organized by target as well as therapeutic area drug classes. It covers existing drugs, and the discovery process that led to their development. Aimed at students and professionals interested in drug discovery, Medicinal Chemistry requires little prior knowledge, making it ideal for classroom and training seminar use. Written by experts in the field, this outstanding new edition explains medicinal chemistry on chemical mechanism terms, allowing for a more interesting and user friendly text. Includes valuable insights towards the various pathways taken by the pharmaceutical industry in drug discoveries. Enhanced text includes questions raised and suggestions made from students in the authors' medicinal chemistry class. Content provided to enhance the text includes a solutions manual, PowerPoint slides for lecture outlines and, especially for the earlier chapters, a selection of videos An accompanying website will be updated to include additional material: a. Journal Club exercises: current journal articles with guiding questions for student analysis (two per chapter) b. Additional case studies c. Organic synthesis analysis: selected syntheses, both discovery and process, will be discussed d. Updates on current advances in the field of Medicinal Chemistry" Benefits a diverse audience including upper level undergraduates and graduates who are studying in the fields of medicinal chemistry and drug discovery, as well as scientists working in the pharmaceutical industry.

  PublisherDOI

• Antiviral and Antifungal Agents

  Garland Science eBooks · 2025-10-30

  book-chapterSenior author
  PublisherDOI

• Anti-Cancer Drugs

  Garland Science eBooks · 2025-10-30

  book-chapterSenior author
  PublisherDOI

• Historical Perspective and Overview of Drug Discovery

  Garland Science eBooks · 2025-10-30

  book-chapterSenior author
  PublisherDOI

• The Process of Developing a Drug from an Optimized Lead

  Garland Science eBooks · 2025-10-30

  book-chapterSenior author
  PublisherDOI

Recent grants

• Therapeutic Optimization of Productive Repair After Acute Kidney Injury

  NIH · $3.2M · 2020–2025

Frequent coauthors

• Amos B. Smith

  University of Pennsylvania

  55 shared

• Peter Wipf

  University of Pittsburgh

  50 shared

• Carlo Ballatore

  Center for Discovery

  40 shared

• Kurt R. Brunden

  University of Pennsylvania

  34 shared

• Michael J. James

  University of Manchester

  28 shared

• Craig J. Thomas

  25 shared

• Paul A. Johnston

  University of Pittsburgh

  25 shared

• Van Tran

  24 shared

Awards & honors

• Fellow of the American Association for the Advancement of Sc…
• Fellow of the American Chemical Society (ACS)
• ACS Philadelphia Local Section Award
• Philip S. Portoghese Lectureship
• Inducted into the ACS Medicinal Chemistry Division Hall of F…