Jian Wei, Ph.D.

Postdoctoral Associate

Studies the impact of metabolic pathways and environments on function of immune cells during homeostasis and diseases.

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About Jian Wei, Ph.D.

My background is in lipid metabolism with a focus on exploring genetic reasons and mechanisms of cholesterol homeostasis and metabolic diseases. Currently I have a keen interest in metabolic regulation of immune system. Besides providing energy and fundamental substrates for survival and growth, metabolic pathways and metabolites control fate decision, differentiation, and effector functions of immune cells. We are investigating the role of metabolic evens within immune cells and elucidating how this impacts immune response outcome. In addition, our study lies at how conditions within the tumor microenvironment shape the metabolism and function of immune cells, thereby suppressing immune response. Ultimately, we aim to develop genetic and pharmacological approaches manipulating immune cell metabolism to improve treatment of cancer and immunological diseases.

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Education and experience

Education

Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Ph.D., Biochemistry and Molecular Biology
Adv: Dr. Bao-Liang Song
2009-2015

Shandong University
B.A., biology
2005-2009

Experience

The Jackson Laboratory
Postdoctoral associate
2018-present

Wuhan University
Postdoctoral associate
2015-2017

Selected Publications

Highlighted Abstract

Cholesterol biosynthesis is tightly regulated in the cell. For example, high sterol concentrations can stimulate degradation of the rate-limiting cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, HMGCR). HMGCR is broken down by the endoplasmic reticulum membrane-associated protein complexes consisting of insulin-induced genes (Insigs) and the E3 ubiquitin ligase gp78. Here we found that HMGCR degradation is partially blunted in Chinese hamster ovary (CHO) cells lacking gp78 (gp78-KO). To identify other ubiquitin ligase(s) that may function together with gp78 in triggering HMGCR degradation, we performed a small-scale short hairpin RNA-based screening targeting endoplasmic reticulum-localized E3s. We found that knockdown of both ring finger protein 145 (Rnf145) and gp78 genes abrogates sterol-induced degradation of HMGCR in CHO cells. We also observed that RNF145 interacts with Insig-1 and -2 proteins and ubiquitinates HMGCR. Moreover, the tetrapeptide sequence YLYF in the sterol-sensing domain and the Cys-537 residue in the RING finger domain were essential for RNF145 binding to Insigs and RNF145 E3 activity, respectively. Of note, amino acid substitutions in the YLYF or of Cys-537 completely abolished RNF145-mediated HMGCR degradation. In summary, our study reveals that RNF145, along with gp78, promotes HMGCR degradation in response to elevated sterol levels and identifies residues essential for RNF145 function.

View full list of publications

Search MagazineMarch 19, 2019
Making a difference for rural cancer patients
Dr. Jens Rueter and the Maine Cancer Genomics Initiative are providing advanced genomic tools to oncology practices throughout Maine.
Research HighlightMarch 08, 2019
Long-range connectivity and gene regulation networks
A complicated three-dimensional network involving proteins and specific DNA sequences helps regulate the expression of genes. New work led by JAX’s Chia-Lin Wei shows how one protein, SOX2, plays a significant role in neural stem cells, affecting many aspects of development and function.
Search MagazineMarch 06, 2019
From tragedy, hope and closure
Doctors who treat rare pediatric cancers face an awful truth: many of their patients will die far too young.
- Cancer/Tumors
- Cancer
Press ReleaseMarch 05, 2019
JAX receives grant to learn why flu vaccines are less effective in the elderly
$2.8 million federal grant to The Jackson Laboratory (JAX) to understand the aging-related genomic changes in immune cells that affect responses to flu vaccines.

Research HighlightMarch 12, 2019
A closer look at structural variants in the genome
A recent Cell paper uses long-read DNA sequencing and other advanced genomics tools and methods to shed light on genomic structural variants.
Research HighlightMarch 08, 2019
Breaking up is hard to do
New research shows that proteins work together to enable DNA double-strand breaks during meiosis.
- Reproductive Biology
- Genetics and Genomics
Search MagazineMarch 06, 2019
Finding a better way to fight childhood cancers
Ching Lau is working to find effective therapies and test them against patients’ own tumors in specially made patient derived xenotype (PDX) mice.
Press ReleaseMarch 05, 2019
3D genomics one nucleus at a time
Supported by a recent four-year, $2.3M grant from the National Institute of General Medical Sciences, Wei is looking to develop a method for chromatin interaction analysis in single nuclei, with single-molecule resolution.
- Genetic Tools
- Genetics and Genomics