The NguyenLab, led by PI David Nguyen, is located within the Center for Translational Genomics at the Innovative Genomics Institute on the UC Berkeley Campus.

Our research interests lie at the intersection of human immunology, infectious diseases, human genome engineering, and gene therapy. Our goal is to leverage the latest technologies in gene editing to understand how mutations cause human diseases of the immune system and to advance gene correction therapies to treat patients with a Primary Immunodeficiency (PID).

Background

Each year thousands of patients develop life-threatening infections, crippling autoimmunity, or other manifestations of an inborn error of immunity that are poorly understood and difficult to treat. Early PID diagnosis is paramount for prognosis, counseling, and treatment success. Sadly, a causative mutation remains elusive for many patients despite genome sequencing because of an inability to distinguish the truly damaging mutations from the numerous (often benign) genetic sequence variants of unknown significance (VUS). While mutations in over 430 different genes have been shown to cause some form of PID disease, each individual patient’s specific mutation is rare, unlikely to be previously investigated, and thus difficult to identify without further functional lab-based studies.

Instead of relying upon genetically dissimilar animal or cancerous cell lines, the NguyenLab leverages gene editing in primary human immune cells to create more pertinent models of disease. Recreating PID patient’s VUS mutations directly in primary human immune cells provides valuable insight into the genetic underpinnings of the human immune response, could uncover novel mechanisms of immune function, and helps us to ultimately develop curative cell and gene therapies.

Approach

The NguyenLab is founded upon continuous improvements in genome engineering technologies in primary human cells. As we build better gene-editing platforms, we are addressing unmet needs for helping patients with PID diseases:

1. Genome engineering in primary human cells to recreate, identify, and diagnose patient-specific PID mutations
2. Functional CRISPR screens to understand and predict how PID mutations impact immune cell behavior
3. Correcting pathogenic mutations in the immune and blood (hematopoietic) system – including PIDs and hemoglobinopathies

We are currently investigating three disease areas:

1. Severe combined immunodeficiency (SCID) and immune regulatory disorders (PIRDs) due to mutations in the interleukin receptor – JAK – STAT signal transduction pathways
2. Mutations causing familial hemophagocytic lymphohistiocytosis (HLH) syndromes.
3. Mutations pertinent to correcting hemoglobinopathies particularly sickle cell disease

Current Projects

News

Grantees probe biology to aid primary immunodeficiency diagnosis — August 29, 2024

The Immune Deficiency Foundation announced funding of four research projects totaling more than $150,000 through the 2024 IDF Research Grant Program. The funded projects each work towards reducing the time to diagnosis for those with primary immunodeficiencies, including a NguyenLab project studying genetic variants of JAK3 and severe combined immunodeficiency (SCID).

Innovative Genomics Institute and Danaher Join Forces to Accelerate and Scale Up the Development of CRISPR Cures — January 9, 2024

The new Beacon for CRISPR Cures collaboration between the IGI and Danaher Corporation aims to create a roadmap for rapidly developing genome-editing therapies. The project is starting with developing CRISPR-based therapies for two inborn errors of immunity, and the NguyenLab is a key part of this work.

New Approach to CRISPR Delivery Opens the Door to Editing Multiple Genes Safely — April 25, 2023

Covering: Foss DV, Muldoon JJ, Nguyen DN, Carr D, Sahu SU, Hunsinger JM, Wyman SK, Krishnappa N, Mendonsa R, Schanzer EV, Shy BR, Vykunta VS, Allain C, Li Z, Marson A, Eyquem J, and Wilson RC. 2023. Peptide-mediated delivery of CRISPR enzymes for the efficient editing of primary human lymphocytes. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-023-01032-2

Recruiting

• We are actively seeking candidates for post-doctoral scientists, research assistants, and graduate students. If you are excited by our work and interested in joining the group, please reach out to David (PI): david[dot]n[dot]nguyen[at]berkeley.edu

Commitment to DEI

• The NguyenLab is eager to engage, support, and train the next generation of scientists and clinicians. All are welcome in our lab — regardless of race, ethnicity, gender identity, sexual orientation, socioeconomic background, or disability. We believe that diversity is a critical component of the educational experience, for maximizing innovative and translational science, and improving patient care and outcomes.
• We foster training programs and personal relationships to promote inclusion of all. We strive to ensure equity and access across all backgrounds and identities, and we are committed to recruiting, mentoring, and training people historically underrepresented in academia and the STEM fields.