About

Prashant Mali, Ph.D., is a Professor in Bioengineering at UCSD. The page lists him as the head of the Mali Lab and includes his title and affiliation, but does not provide specific details about his research focus, background, or key contributions.

Research topics

• Biochemistry
• Biology
• Internal medicine
• Genetics
• Endocrinology
• Medicine
• Cell biology
• Computational biology

Selected publications

• Receptor-guided AAV Tropism Engineering via MATCH

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-01

  articleOpen accessSenior authorCorresponding

  Precise control over viral tropism remains a major challenge in the development of gene delivery technologies. We present MATCH (Modulation of AAV Tropism through Conjugation to Homing proteins), a modular biochemical method that enables programmable, receptor-guided retargeting of adeno-associated viruses (AAVs) through site-specific covalent protein conjugation. By incorporating a SpyTag peptide motif into selected AAV capsid loops, MATCH allows one-step, stoichiometrically defined attachment of recombinant SpyCatcher-linked targeting proteins to the viral surface. Using mosaic AAV-DJ and AAV9 capsids with controlled SpyTag incorporation, we achieve efficient assembly and tunable ligand display. MATCH-AAVs conjugated to an anti-CD3 single-chain antibody efficiently activate and transduce resting human T cells within mixed PBMC populations in vitro, achieving transduction levels of up to ~58% of total PBMCs. Conjugation to transferrin receptor (TfR1)-binding proteins yielded enhanced brain transduction in vivo, with murine TfR1-targeted MATCH-AAV9 exhibiting up to an 84-fold increase in brain expression relative to wild-type AAV9. Human TfR1-targeted vectors similarly enabled robust, receptor-dependent transduction both in vitro and in humanized mouse models. Both TfR-targeted vectors enabled widespread transduction of the parenchyma, consistent with TfR1-mediated crossing of the blood-brain barrier. Finally, we establish a streamlined one-pot "Mix-and-MATCH" production strategy in which capsid and targeting ligands are co-expressed during vector generation, yielding functional, targeted AAVs at titers comparable to conventional production. This simple and generalizable synthetic-biology approach provides a versatile toolkit for rational AAV tropism engineering, offering a scalable route to custom vector design for research and therapeutic applications.

  PublisherDOI

• Supplementary Figure 1 from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <p>Supplementary Figure 1. Genome-wide CRISPR-Cas9 screen identifies PKA signaling as a metformin resistance pathway in HNSCC. (Related to Figure 1)</p>

  PublisherDOI

• Supplementary Figure 5 from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <p>Supplementary Figure 5. Combination of metformin with NSAIDs, which inhibit COX2, enhances the inhibition of HNSCC cell growth in vitro. (Related to Figure 3)</p>

  PublisherDOI

• Supplementary Figure 2 from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <p>Supplementary Figure 2. Activation of PKA in HNSCC cells reduces sensitivity to metformin growth inhibition in vivo. (Related to Figure 1)</p>

  PublisherDOI

• Supplementary Figure 6 from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <p>Supplementary Figure 6. Squamous cell carcinoma (SCC)-positive tongues from the metformin + naproxen treatment arm. (Related to Figure 4)</p>

  PublisherDOI

• Supplementary Figure 3 from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <p>Supplementary Figure 3. Combination of metformin with NSAIDs, which inhibit COX2, enhances the inhibition of HNSCC cell growth in vitro. (Related to Figure 3)</p>

  PublisherDOI

• Abstract 1287: A spatiotemporal proteome map of chemotherapy response in metastatic breast cancer

  Cancer Research · 2026-04-03

  article

  Abstract Cells are not simply aggregates of molecules; they are highly organized entities with dynamic structures and functions that evolve in response to external stimuli, such as drug treatments. Understanding how tumor cells reorganize these structures and functions, both spatially and temporally, is essential for unraveling the mechanisms underlying tumor behaviors including treatment response. Through the NIH Bridge2AI Cell Maps for AI (CM4AI) data generation project, we profiled spatiotemporal proteomics in metastatic breast cancer cells across untreated and chemotherapy-treated conditions using complementary proteomics technologies: immunofluorescence imaging (∼11,000 images covering >100,000 single cells to map subcellular localization of >500 proteins), mass spectrometry (protein interactions of >500 proteins and complex organization across >5000 proteins), and single-cell CRISPR sequencing (>120,000 single-cell transcriptomes across 200 gene perturbations). Using self-supervised contrastive learning, we fuse protein embeddings across modalities while preserving treatment-induced protein dynamics. Our analyses reveal that chemotherapy triggers substantial protein reorganization. For example, in untreated cells, HDAC8 forms an assembly in close proximity to TET1, SETDB2, PHF6 and YWHAG. However, after paclitaxel treatment, its expression increases substantially and relocates from cytosol to nucleus. It forms a new seven-protein assembly with PARP1, KAT6B, DNMT3A, HDAC9, HDAC2, and BRD4. Building on this foundation, we will construct an integrated map that (a) delineates how individual proteins assemble into complexes and higher-order structures; (b) annotates these subcellular components with their functional states; and (c) models the dynamics of specific cellular components across drug treatment contexts. Citation Format: Xiaoyu Zhao, Jiahao Gao, Gege (Scarlett) Qian, Richa Tiwari, Jan N. Hansen, Antoine Forget, Sami Nourreddine, Yesh Doctor, Jillian Parker, Prashant Mali, Nevan Krogan, Emma Lundburg, Trey Ideker. A spatiotemporal proteome map of chemotherapy response in metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1287.

  PublisherDOI

• Data from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <div>Abstract<p>Head and neck squamous cell carcinoma (HNSCC) is among the 10 most common cancers worldwide and is associated with high morbidity and poor survival. Diminished HNSCC outcomes are often related to delayed diagnosis and treatment of occult progression of premalignant lesions, underscoring the need for effective and low-risk chemoprevention strategies. In this regard, metformin has shown promising clinical activity for HNSCC prevention. In this study, we performed a genome-wide CRISPR/Cas9 screen of metformin-treated HNSCC cells and identified the activation of PKA signaling as the top resistance pathway. We show that metformin mediates PKA activation in HNSCC cells and that PKA inhibition, when combined with metformin treatment, synergistically inhibits HNSCC growth. We found that metformin-induced PKA activation is mediated by a prostaglandin E<sub>2</sub> autocrine loop, which can be blocked using cyclooxygenase-2 (COX2) inhibitors. Importantly, COX2 inhibition using nonsteroidal anti-inflammatory drugs (NSAID) combined with metformin treatment synergistically inhibits HNSCC cell growth and prevents the progression of oral premalignant lesions into invasive HNSCC in a model of tobacco-driven oral carcinogenesis. Together, these findings demonstrate that metformin and NSAID combination therapy may represent a promising therapeutic strategy for HNSCC chemoprevention.</p>Prevention Relevance:<p>Our findings reveal that using metformin for head and neck cancer chemoprevention leads to compensatory activation of a PKA-driven resistance mechanism that can be blocked by cotreatment with NSAIDs. These findings provide a rationale for combining metformin with NSAIDs as a precision head and neck cancer chemoprevention strategy.</p></div>

  PublisherDOI

• Supplementary Table 1 from Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs

  2026-02-06

  articleOpen access

  <p>Supplementary Table 1. PKA-related resistance driving hits selected from the metformin CRISPR screen.</p>

  PublisherDOI

• Abstract 7637: Genome-wide CRISPR screening reveals a PKA-driven resistance mechanism to metformin for oral cancer prevention that can be exploited by combination with NSAIDs

  Cancer Research · 2026-04-03

  article

  Abstract Head and neck squamous cell carcinoma (HNSCC) is among the ten most common cancers worldwide and is associated with high morbidity and poor survival. Diminished HNSCC outcomes are often related to delayed diagnosis and treatment of occult progression of premalignant lesions, underscoring the need for effective and low risk chemoprevention strategies. In this regard, metformin has shown promising clinical activity for HNSCC prevention. Here, we performed a genome-wide CRISPR/Cas9 screen of metformin-treated HNSCC cells and identified activation of PKA signaling as the top resistance pathway. We show that metformin mediates PKA activation in HNSCC cells, and that PKA inhibition (PKAi) when combined with metformin treatment synergistically inhibits HNSCC growth. We found that metformin-induced PKA activation is mediated by a prostaglandin E2 (PGE2) autocrine loop, which can be blocked using cyclooxygenase-2 (COX2) inhibitors. Importantly, COX2 inhibition using non-steroidal anti-inflammatory drugs (NSAIDs) combined with metformin treatment synergistically inhibits of HNSCC cell growth and prevents progression of oral premalignant lesions (OPLs) into invasive HNSCC in a model of tobacco driven oral carcinogenesis. Together, these findings demonstrate that metformin and NSAID combination therapy may represent a promising therapeutic strategy for HNSCC chemoprevention. Citation Format: Thomas S. Hoang, Farhoud Faraji, Amaya Mendez-Molina, Sendi R. Adame-Garcia, Kuniaki Sato, Tomohiko Ishikawa, Pham Thuy Vo, Sydney Ramirez, Paola Y. Anguiano Quiroz, Tracy Guo, Katie Fan, Xingyu Wu, Alfredo Molinolo, Ezra E. W. Cohen, Prashant Mali, Scott M. Lippman, J. Silvio Gutkind. Genome-wide CRISPR screening reveals a PKA-driven resistance mechanism to metformin for oral cancer prevention that can be exploited by combination with NSAIDs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7637.

  PublisherDOI

Recent grants

• Systematic mapping of genetic vulnerabilities in head and neck cancer

  NIH · $1.4M · 2017–2023

• Dissecting the interplay of gene regulatory networks and cellular niche on cell fate determination

  NIH · $1.2M · 2018–2023

• Bridge2AI: Cell Maps for AI (CM4AI) Data Generation Project

  NIH · $21.0M · 2022–2026

• Next-generation Functional Genetic Screening of Un-screenable Traits

  NIH · $4.2M · 2017–2022

Frequent coauthors

• Linzhao Cheng

  Johns Hopkins Medicine

  82 shared

• Kyle Ford

  University of California, San Diego

  47 shared

• Zhaohui Ye

  Harbin Institute of Technology

  46 shared

• J. Silvio Gutkind

  University of California, San Diego

  31 shared

• Nadia Arang

  Quantitative BioSciences

  29 shared

• Jonathan Yen

  St. Jude Children's Research Hospital

  29 shared

• Xingyu Wu

  28 shared

• Keiichi Koshizuka

  27 shared

Labs

• Mali LabPI

  Not provided

Awards & honors

• Siebel Scholar Award
• Burroughs Wellcome Career Award
• March of Dimes Basil O’Conner Scholar Award
• Kimmel Scholar Award
• Kavli Frontiers of Science Fellow