About

Matthew B. Francis is the Aldo DeBenedictis Distinguished Professor of Chemistry at the University of California, Berkeley. He was born in 1971 and earned his B.S. in Chemistry from Miami University in 1994. He completed his Ph.D. in Organic Chemistry at Harvard University in 1999 under the supervision of Professor Eric N. Jacobsen. Following his doctoral studies, he was a Postdoctoral Fellow at the Miller Institute for Basic Research in Science at UC Berkeley, working with Professor Jean M. J. Fréchet from 1999 to 2001. Professor Francis's research focuses on organic, bioorganic, and materials chemistry, particularly on the development of new synthetic methods for the construction of nanoscale materials. His work involves attaching functional components to specific locations on structural proteins and enabling their self-assembly into materials with electronic and biological functions. His research includes the controlled growth of nanocrystalline arrays using cytoskeletal proteins, the synthesis of three-dimensional nanostructures from self-assembling viral capsids, and the development of new methods for site-specific protein modification. His contributions aim to advance the understanding and application of nanomaterials, with potential uses in optical, electronic, and biomedical fields.

Research topics

• Chemistry
• Social Science
• Combinatorial chemistry
• Political Science
• Sociology
• Organic chemistry
• Biochemistry
• Medicine
• Stereochemistry
• Ecology
• Public relations
• Chromatography
• Psychology
• Medical education
• Physical chemistry
• Chemical physics

Selected publications

• Abstract 6928: Dual-payload antibody drug conjugate targeting TROP2: Multi-Payload Conjugates™ targeting orthogonal mechanisms of cell killing

  Cancer Research · 2026-04-03

  article

  Abstract Introduction: Antibody-Drug Conjugates (ADCs) have a tremendous impact on patient outcomes in breast and other cancers. Dato-DXd, for example, is a 2nd-line therapy for stage IV, HR+/HER2 negative metastatic breast cancer and EGFR mutant non-small cell lung cancer (NSCLC). Sacituzumab govitecan (SG), is approved as a 3rd line therapy in metastatic HER2 negative breast cancer. Many patients fail to respond or relapse after treatment with these ADCs due to tumor heterogeneity and resistance to the mono payload ADC. Dosing in patients is further limited by off-target toxicity due to instability of the maleimide bond between the antibody and linker. Combination therapies have historically outperformed monotherapies across most solid tumors, pointing to a potential for improvement of ADC efficacy. CatenaBio is developing next generation Multi-Payload Conjugates™ (MPCs™) with dual payloads and a more stable C-Y bond, that deliver targeted combination chemotherapies within a single molecule with reduced toxicities to address shortcomings in current ADCs. Method: CatenaBio has developed highly stable, dual-payload ADC combination therapies, with tunable payload ratios. Our selective conjugation platform allows the attachment of distinct payloads targeting different mechanisms of action at three unique sites on antibody scaffolds replacing the unstable maleimide bond with a more stable C-Y bond. Results: Catena’s lead TROP2 targeting dual payload MPC, CATB-101, features an optimized combination and ratio of tubulin and TOP1 inhibitors. CATB-101 demonstrates superior tumor growth inhibition and excellent tolerability in multiple TROP2 expressing CDX and PDX models of TNBC, gastric, and lung cancers. In head-to-head comparisons, CATB-101 outperforms T-DXd, SG and Dato-DXd with full tumor elimination at low doses. CATB-101 eliminates tumors in models following progression on SG treatment, demonstrating potential in ADC relapsed patients. Non-GLP non-human primate (NHP) toxicology trials with CATB-101 demonstrate a remarkable safety profile, by eliminating or reducing off-target toxicity. Conclusion: Advances have been made in the design of ADCs to expand to previously unaddressed populations. High patient relapse and the failure of recent mono-payload ADCs in late-stage trials indicate a need for next generation multi-payload conjugates. Catena’s MPCs™ offer a next step in ADC design and allow for targeted delivery of multiple mechanisms of action with a single MPC™ while reducing off-target toxicity. CATB-101 is highly efficacious at eliminating tumors across multiple CDX and PDX models of cancer that display a range of target surface expression. Validated in early NHP toxicology studies with a significantly enhanced therapeutic window, these molecules offer the potential to circumvent tumor resistance pathways to deliver more durable patient responses. Citation Format: Marco Lobba, Samantha Brady, Devin Trinter, Maxwell Nguyen, Chanez Symister, Andrew Lau, Derek Garcia-Almedina, Charlotte Choi, Saurabh Johri, Matthew Francis, Richard Kendall. Dual-payload antibody drug conjugate targeting TROP2: Multi-Payload Conjugates™ targeting orthogonal mechanisms of cell killing [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 6928.

  PublisherDOI

• Biosynthesis of Minimal C-Phycocyanin Chromophore Assemblies in <i>E. coli</i> Provides a Platform to Dissect Protein-Mediated Tuning of Exciton Transfer

  Journal of the American Chemical Society · 2026-01-12

  articleSenior authorCorresponding

  Cyanobacteria are arguably among the most evolutionarily successful organisms on Earth, inhabiting a wide range of ocean, freshwater, soil, and even desert environments on every continent. The cyanobacterial phycobilisome consists of stacks of disk-like light-collecting moieties, allophycocyanin (APC) and phycocyanin (CPC), with covalently bound phycocyanobilin (PCB) pigments. The ways in which the energies of the specific chromophores in these complexes are tuned by the protein to achieve its highly efficient and directional energy transfer are not fully understood, as complex combinations of decay pathways are occurring simultaneously and competitively through this elaborate light-harvesting system. This makes it difficult to extract information about isolated protein-pigment interactions. We provide herein a description of a useful new experimental platform in which we have recombinantly expressed a fully functioning CPC complex and selectively created minimal chromophore sets to study their individual contributions to the overall CPC spectra. Structural and computational analysis of this protein system have provided a greater understanding of how the protein environment serves to alter the photophysics of each of these chromophores. Introduction of a quencher into various positions within CPC confirmed the ability of the protein environment to tune the directionality of energy transport in this assembly. Further mutational analysis suggested the roles of key amino acids surrounding the chromophores, showcasing the utility of heterologous expression techniques for understanding the effects of structure on EET mechanisms in the phycobilisome.

  PublisherDOI

• Cytosolic Delivery of Anionic Cyclic Dinucleotide STING Agonists with Locally Supercharged Viral Capsids

  ACS Chemical Biology · 2025-07-29 · 2 citations

  articleSenior authorCorresponding

  Cyclic dinucleotide (CDN) STING agonists represent a powerful new immunotherapy treatment modality and are a class of nucleotide-based therapies with broad clinical potential. However, they face practical challenges in administration, largely due to their poor pharmacological properties. We report the development of a drug delivery platform for CDNs and other anionic small-molecule drugs using bacteriophage MS2 viral capsids with engineered cationic residues. Relative to viral capsids lacking locally supercharged regions, these assemblies exhibit substantial increases in mammalian cell uptake while avoiding cell toxicity and hemolysis. A synthetic strategy was developed to attach CDN drugs covalently to the interior capsid surfaces through reductively cleavable disulfide linkers, which allowed for traceless drug release upon cell entry and exposure to reductive cytosolic environments. MS2-mediated CDN delivery into immune cell populations resulted in an approximately 100-fold increase in delivery efficiency compared with free drugs and showed enhanced STING activation as well as downstream cytokine release.

  PublisherDOI

• Site-selective protein editing by backbone extension acyl rearrangements

  Nature Chemical Biology · 2025-08-21 · 5 citations

  article
  PublisherDOI

• A Dragonfly for Titan

  Eos · 2025-02-14

  articleOpen access1st authorCorresponding

  A new eight-rotor robotic probe will head to the solar system’s most Earth-like moon. Here’s what its team is doing to prepare.

  PublisherDOI

• Introduction of Reactive Thiol Handles into Tyrosine-Tagged Proteins through Enzymatic Oxidative Coupling

  Journal of the American Chemical Society · 2025-06-27 · 5 citations

  articleOpen accessSenior authorCorresponding

  Site-specific protein bioconjugation methods have enabled the development of new therapeutics and materials, and further development of existing techniques has expanded the compatible library of protein substrates for bioconjugation. Among these techniques, the enzyme tyrosinase has demonstrated a promising ability to form protein–protein conjugates between exposed tyrosine and cysteine residues. In this work, we observed that the tyrosinase variant from Bacillus megaterium, termed megaTYR, has an increased tolerance for small-molecule thiol substrates, which can inhibit the activity of other tyrosinases. Among the breadth of thiol substrates that could be reliably coupled to tyrosine-tagged proteins was dithiothreitol (DTT), which effectively introduces a free thiol handle and provides a convenient method to bypass the genetic incorporation of cysteine residues for bioconjugation. Accordingly, these thiolated proteins could undergo additional coupling to commercially available maleimide probes as well as other tyrosine-tagged proteins. This was demonstrated by the conjugation of targeting proteins to drugs, fluorescent probes, and therapeutic enzymes. Of particular note and building on a previous report of a tyrosinase-sensitive tyrosine residue on the Fc region of antibodies, commercially available monoclonal antibodies (mAbs) treated with PNGase F were conjugated to DTT to produce THIOMAB equivalents. These intermediates were subsequently used to make functional antibody–drug and antibody–toxin protein conjugates. This facile method to convert accessible tyrosine residues on proteins to thiol tags extends the use of tyrosinase-mediated oxidative coupling to a broader range of protein substrates.

  PublisherDOI

• Abstract P4-04-27: Next generation antibody drug conjugates targeting HER2 and TROP2: Multi-Payload Conjugates™ targeting orthogonal mechanisms of cell killing

  Clinical Cancer Research · 2025-06-13

  articleSenior author

  Abstract Introduction: Antibody-Drug Conjugates (ADCs) have had tremendous impact on patient outcomes in breast cancer and are now second-line therapy for stage IV HER2 high expressing metastatic breast cancer as well as HER2 low expressing tumors. However, many patients fail to respond or relapse after treatment with ADC therapies due to tumor heterogeneity and eventual resistance to the ADC payload. We are developing next generation Multi-Payload Conjugates™ (MPCs™) that deliver targeted combination chemotherapies within a single molecule. Method: CatenaBio has developed novel, highly stable single-molecule targeted combination therapies, MPCs™, with tunable drug-antibody ratio (DAR). Our selective conjugation platform allows the attachment of distinct payloads targeting different mechanisms of action at three unique sites on the antibody scaffold. Results: We screened combinations of different payloads targeting several different mechanisms of cell division attached to trastuzumab as well as sacituzumab at different DARs to optimize tumor cell killing. These targeted combination ADCs demonstrated robust killing in multiple cell lines containing high and low expression of HER2 and TROP2, as well as an Enhertu resistant cell line. Additionally, these novel MPCs show potent inhibition and excellent tolerability in mouse models of tumor growth in HER2 high and HER2 low/TROP2 expressing xenograft models including models of TNBC. Conclusion: While advances have been made in the design of ADCs to expand to previously unaddressed populations, high patient relapse and the failure of recent mono-payload ADCs in late-stage trials indicate a need for novel conjugate modalities. Multi-payload Conjugates™ offer the next step in ADC design and allow for the combination of multiple mechanisms of action in a single MPC™ that are highly effective across multiple breast cancer cell lines and target expression levels. Successfully constructed with both HER2 and TROP2 targeting antibodies, these molecules offer the potential to circumvent tumor resistance pathways and deliver deeper and more durable patient responses. Citation Format: Marco Lobba, Richard Kendall, Devin Trinter, Maxwell Nguyen, Daniel Gutierrez, Samantha Brady, Chanez Symister, Andrew Lau, Derek Garcia-Almedina, Saurabh Johri, Matthew Francis. Next generation antibody drug conjugates targeting HER2 and TROP2: Multi-Payload Conjugates™ targeting orthogonal mechanisms of cell killing [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-04-27.

  PublisherDOI

• Integrating social responsibility and diversity, equity, and inclusion into the graduate chemistry curriculum

  Chemical Science · 2025-01-01 · 4 citations

  articleOpen access

  Science's broader impacts and the historic social, political, and geographic implications of these impacts are rarely discussed in graduate STEM curricula. A new required "Scientific Responsibility and Citizenship" course for first year chemistry graduate students was developed and taught at UC Berkeley. The course examined a series of case studies in which basic chemistry research led to societal impacts and discussed the diversity and equity of the research process and resulting consequences. The impact of the course was examined through pre- and post-surveys and interviews with participants. The course was found to have raised students' awareness and sense of responsibility for the impacts of their research and the importance of diversity, equity, and inclusion. Students also expressed an increased sense of identity and value alignment with the community as a result of the course. This study shows that even a relatively low-commitment intervention (6 hours in total), can have a large positive impact on students' awareness of the social context of science and their perceptions of department values.

  PublisherOA PDFDOI

• Engineered MS2 Virus Capsids for Cellular Display of Peptide Antigens

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-19

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Our ability to respond to emerging pandemics and pathogen resistance relies critically on our ability to build vaccines quickly and efficiently. In this report we used an efficient enzymatic oxidative coupling reaction to create a viral capsid-based vaccine platform that is modular and quickly adaptable for many different pathogens. Tyrosinase-mediated oxidative coupling was used to conjugate C-terminal tyrosine residues on peptide antigens to cysteine residues installed inside MS2 viral capsids. This strategy is particularly promising because the capsids protect the internally conjugated peptides from protease degradation before they are delivered into cells. The vaccine constructs were tested for MHC presentation followed by T-cell activation. Mutants of the MS2 capsid itself activated DC2.4 cells, serving as an adjuvant to help induce the immune response to delivered antigens. The MS2-peptide constructs were shown to be stable in serum, activate DC2.4 cells, and lead to MHC-presentation of peptide antigens with subsequent activation of antigen-specific T-cell hybridomas. Taken together, these results demonstrate effective activation of the adaptive immune system in vitro . This synthetic platform can be used to build new vaccines for many different diseases for which immunodominant peptide antigens are known because the antigens can be quickly interchanged while the MS2 scaffold remains the same. Additionally, this platform allows for multiple peptide antigens to be delivered simultaneously in each capsid, which could provide enhanced immunity against resistant strains and be useful for cancer vaccine development.

  PublisherOA PDFDOI

• Biosynthesis of minimal C-phycocyanin chromophore assemblies in <i>E. coli</i> provides a platform to dissect protein-mediated tuning of exciton transfer

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-15

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Cyanobacteria are arguably among the most evolutionarily successful organisms on Earth, inhabiting a wide range of ocean, fresh water, soil, and even desert environments on every continent. The cyanobacterial phycobilisome consists of stacks of disk-like light-collecting moieties, allophycocyanin (APC) and phycocyanin (CPC), with covalently bound phycocyanobilin (PCB) pigments. The ways in which the energies of the specific chromophores in these complexes are tuned by the protein to achieve its highly efficient and directional energy transfer are not fully understood, as complex combinations of decay pathways are occurring simultaneously and competitively through this elaborate light-harvesting system. This makes it difficult to extract information about isolated protein-pigment interactions. We provide herein a description of a useful new experimental platform in which we have recombinantly expressed a fully functioning CPC complex and selectively created minimal chromophore sets to study their individual contributions to the overall CPC spectra. Structural and computational analysis of this protein system have provided a greater understanding of how the protein environment serves to alter the photophysics of each of these chromophores. Introduction of a quencher into various positions within CPC confirmed the ability of the protein environment to tune the directionality of energy transport in this assembly. Further mutational analysis suggested the roles of key amino acids surrounding the chromophores, showcasing the utility of heterologous expression techniques for understanding the effects of structure on EET mechanisms in the phycobilisome.

  PublisherOA PDFDOI

Recent grants

• Synthesis of Polymer-Protein Hybrid Materials Using Site Selective Protein Modification Reactions

  NSF · $422k · 2011–2014

• CAREER: Synthetically Modified Tobacco Mosaic Virus: A Versatile Scaffold for Nanoscale Materials

  NSF · $450k · 2005–2010

• CAREER: Toward the Creation of Custom Bacterial Organelles from Engineered /Salmonella/ Pdu Bacterial Microcompartments

  NSF · $528k · 2012–2017

• Facile Generation of Protein-Protein Conjugates Using Enzymatic Oxidative Coupling Reactions

  NIH · $1.5M · 2020–2027

• Polymer-Protein Hybrid Materials for the Selective Capture of Water Pollutants

  NSF · $435k · 2014–2018

Frequent coauthors

• David E. Wemmer

  QB3

  65 shared

• Alexander Pines

  University of California, Berkeley

  64 shared

• Carolyn R. Bertozzi

  Stanford University

  49 shared

• Daniel Brauer

  Instituto de Filosofía

  45 shared

• Johnathan C. Maza

  University of California, Berkeley

  43 shared

• Aaron P. Esser‐Kahn

  University of Chicago

  40 shared

• Sonny C. Hsiao

  39 shared

• Jennifer A. Doudna

  University of California, Berkeley

  38 shared

Labs

• Francis Research GroupPI

Awards & honors

• Camille and Henry Dreyfus Foundation New Faculty Award (2001…