Matthew E. Brown, PhD

One Battle After Another has the best cinematic representation of gel electrophoresis ever, hands down.

Establishing a Fixed Time Period of Admission and an Extension of Stay Procedure for Nonimmigrant Academic Students, Exchange Visitors, and Representatives of Foreign Information Media Unlike most nonimmigrant classifications, which are admitted for a fixed time period, aliens in the F (academic student), J (exchange visitor), and most I (representatives of foreign information media...

I encourage everyone in academic science to read these proposed rules and comment on them per the instructions on the Federal Register. www.federalregister.gov/documents/20...

Thanks to Sayandeep Saha, Brown Lab Team members, our collaborators, and funding agencies (this wouldn’t have been possible without the NIH!) #NIH @warfnews.bsky.social‬ ‪
@uwmadisonstemcell.bsky.social‬
@wiscsurgery.bsky.social‬
@morgridgeinstitute.bsky.social‬
www.the-brown-lab.com

We believe ICAM-1 KO PSC will serve as a platform technology, with applications in a number of disease areas. We are looking to collaborate with researchers investigating Parkinson’s, macular degeneration, and hematopoietic and other contexts that require MHC-replete cells.

Islet beta-cells and intercellular adhesion molecule-1 (ICAM-1): Integrating immune responses that influence autoimmunity and graft rejection - PubMed Type 1 diabetes (T1D) develops due to autoimmune targeting of the pancreatic islet β-cells. Clinical symptoms arise from reduced insulin in circulation. The molecular events and interactions between d...

ICAM-1 plays an important role in T1D pathogenesis, and we are eager to explore ICAM-1 KO PSC-islets as a new therapeutic candidate for T1D. pubmed.ncbi.nlm.nih.gov/37619906/

Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes | NEJM Zimislecel is an allogeneic stem cell–derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. We conducted a phase 1–2 study of zimisle...

Our lab is exploring ICAM-1 KO PSCs for cardiovascular disease, as well as Type 1 diabetes (T1D). T1D is a particularly promising area for leveraging this hypoimmune technology, in light of recent clinical advances. www.nejm.org/doi/full/10....

Conventional hypoimmune PSC editing (e.g., MHC KO) can result in an adverse effect—NK cell missing self killing. Our editing approach leaves MHC intact, so we may avoid this adverse effect. Future studies in our lab will explore the role of NK cells against ICAM-1 KO cells.

ICAM-1 is a target involved in multiple aspects of the allograft rejection response, such as 1) immune synapse formation; 2) transendothelial migration; 3) cellular responses to external inflammatory oxidative stress. We are actively exploring these and other roles of ICAM-1 in our lab.

Use of the NeoThy is important for PSC immunogenicity studies, as other humanized mouse models besides the NeoThy and BLT lack human thymus incorporation and are suboptimal for assessing human MHC-restricted T cell responses. pubmed.ncbi.nlm.nih.gov/32588980/ pubmed.ncbi.nlm.nih.gov/37386161/

We transplanted ICAM-1 KO into next-generation NeoThy humanized mice and saw that the KO cells were retained, but wild type cells were dramatically reduced in size, indicating that the KOs are protected against allograft rejection in vivo.

ICAM-1 KO reduced binding of adaptive (e.g., T cells) and innate (e.g., neutrophils) immune cells. It also resulted in markedly diminished T cell activation and proliferation in vitro.

We successfully and reproducibly made three ICAM-1 knock out cardiovascular cell types (endothelial cells, cardiomyocytes, and cardiac fibroblasts) from multiple PSC lines, including induced PSCs and embryonic stem cells.

ICAM-1 is expressed on endothelial and other cells and is upregulated in response to post-transplantation inflammatory stimuli (e.g., TNFa, IFNg). There are cell surface and secreted forms of ICAM-1. Our KO prevented both types of protein from being expressed by the cells.

This work describes a new class of hypoimmune gene edit for pluripotent stem cell (PSC)-based therapies. We used CRISPR-Cas9 gene editing technology to knock out (KO) ICAM-1, an important cell adhesion molecule used by adaptive and innate immune cells mediating transplantation rejection.

Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells Nature Communications - Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion...

I’m excited to share our new manuscript in Nature Communications, Saha et al., “ Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells.” rdcu.be/eAnEC

Canada wildfires force 17,000 to evacuate, with smoke blowing toward U.S. Authorities in Manitoba, which shares a border with the U.S., issued a state of emergency. Winds will likely blow wildfire smoke into Midwestern states.

Wisconsin is about to get smoked www.washingtonpost.com/weather/2025...

Val Kilmer, Film Star Who Played Batman and Jim Morrison, Dies at 65 A wide-ranging leading man who earned critical praise, he was known to be charismatic but unpredictable. At one point he dropped out of Hollywood for a decade.

RIP Val Kilmer, one of the greats.

www.nytimes.com/2025/04/01/m...

Federal Register hold makes ‘end run’ around court pause on NIH funding freeze NIH-related updates to the Federal Register, which are required for the scheduling of study sections and advisory councils, are on hold indefinitely, according to an email reviewed by <i>The Transmitt...

www.thetransmitter.org/funding/fede...

Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups Read online, download a free PDF, or order a copy in print or as an eBook.

Underrepresentation of certain ethnic groups in biomedical research is a real problem. See: nap.nationalacademies.org/catalog/2647...

In recent years, the NIH and others have made efforts to address this. Will this important issue become a causualty of the ongoing anti-DEI efforts?

How a simple math error sparked a panic about black plastic kitchen utensils A study warned that people were being exposed to a toxic chemical from kitchen utensils. But the researchers misstated the safe daily limit

HA

"That sounds bad. But 60 times 7,000 is not 42,000. It is 420,000. This is what Joe Schwarcz noticed. The estimated exposure is not even a tenth of the reference dose. That does not sound as bad."

On black plastic spatulas, and scientific mistakes

nationalpost.com/news/canada/...

Bluesky skeets, not Twitter tweets.