Shingo Kajimura

Shingo Kajimura

Associate Professor of Medicine
Shingo Kajimura
Bioenergetics and Energy Homeostasis
 
My laboratory studies the molecular basis of bioenergetics in health and disease, i.e., how we coordinate metabolic demands and control energy homeostasis, and how the processes go wrong in metabolic diseases, cancer, and aging. The overarching goal is to generate a blueprint for rewiring the bioenergetic circuitry by defined factors, thereby restoring metabolic health.
 
A particular focus in my lab is adipose tissues because it dynamically remodels their cellular composition, metabolism, and function in response to external and internal cues, including nutrition, hormonal cues, and temperature. Such metabolic adaptation in adipose tissues, involving differentiation, mitochondrial biogenesis/clearance, lipolysis/lipogenesis, and thermogenesis, plays a central role in the regulation of whole-body energy homeostasis. In turn, a defect in the processes leads to obesity, insulin resistance, dyslipidemia, cardiovascular diseases, and certain types of cancer.
 
Current focuses in the lab are the following:
 
1) Regulation of bioenergetics by mitochondrial transporters.
The mitochondrion is the center of bioenergetics in eukaryotes. Given the impermeable nature of mitochondrial inner-membrane, a variety of carrier proteins determine the metabolite transport into the matrix. Our lab recently identified the first mitochondrial carrier for branched-chain amino acids (BCAA), a.k.a., mitochondrial BCAA carrier. This carrier protein controls a broad spectrum of pathophysiology, including thermogenesis in brown fat, febrile responses, insulin sensitivity, and cell growth/cancer. We aim to explore the biological roles of this newly identified mitochondrial carrier as well as other uncharacterized transporters.
 
2) Bioenergetics and cellular plasticity
Mitochondrial bioenergetics controls cell fate determination, differentiation, and maintenance. A particular interest in our lab has been the developmental pathway of “inducible” thermogenic brown adipocytes, a.k.a., beige adipocytes. Beige adipocyte development and maintenance are highly regulated by nutritional cues and temperature (e.g., cold). We aim to understand how bioenergetics controls beige adipocyte biogenesis and how the processes are dysregulated in metabolic diseases.
 
3) Developing fat-specific “cold-mimetics” for improving metabolic health.
Cold exposure promotes brown/beige adipocyte biogenesis, leading to a profound improvement in metabolic health, including improved glucose tolerance, insulin sensitivity, and lipid profile. The long-standing dogma in the field was that such metabolic benefit is mediated through enhanced thermogenesis by uncoupling protein 1 (UCP1). Unexpectedly, however, our lab shows that the metabolic benefit of beige fat is UCP1-independent. Accordingly, we aim to uncover the underlying mechanisms and reconstitute the metabolic benefit of brown/beige fat without cold exposure, i.e., fat-specific “cold-mimetics” to improve metabolic health.

Contact Information

Beth Israel Deaconess Medical Center
Division of Endocrinology, Diabetes & Metabolism
3 Blackfan Circle CLS737
Boston, MA 02115
p: 617-735-3289

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