Brian J. North, PhD
School of Medicine
- Biomedical Sciences
- Assistant Professor
Brian J. North is an Assistant Professor in the Biomedical Sciences Department. After receiving his B.A. from Gustavus Adolphus College, he completed his Ph.D. from the University of California San Francisco with Dr. Eric Verdin. He then went on to his postdoctoral fellowship at Harvard Medical School with Dr. David Sinclair, and subsequently was a Research Assistant Professor at Beth Israel Deaconess Medical Center where he worked closely with the lab of Dr. Wenyi Wei. His main research focus is to understand the molecular and cellular pathways involved in regulating the process of aging, and how changes in these pathways contribute to the development of age-related diseases, with a primary interest in tumorigenesis.
Learn more about Dr. North's research.
Learn more about Dr. North's research.
- Ji Cheng, Jianping Guo, Brian J. North, Bin Wang, Chun-Ping Cui, Hongsheng Li, Kaixiong Tao, Lingqiang Zhang and Wenyi Wei. Functional analysis of deubiquitylating enzymes in tumorigenesis and development, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1872, 188-312, 2019
- Ying Ma, Danrui Cui, Xiufang Xiong, Hiroyuki Inuzuka, Wenyi Wei, Yi Sun, Brian J. North,# and Yongchao Zhao#. SCFβ-TrCP ubiquitinates CHK1 in an AMPK-dependent manner in response to glucose deprivation, Molecular Oncology, 13, 307-321, 2019
- Ji Cheng, Jianping Guo, Brian J. North, Kaixiong Tao, Pengbo Zhou, and Wenyi Wei. The emerging role for Cullin 4 family of E3 ligases in tumorigenesis, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1871, 138-159, 2019
- Ji Cheng, Brian J. North, Tao Zhang, Xiangpeng Dai, Kaixiong Tao, Jianping Guo, and Wenyi Wei. The Emerging Roles of Protein Homeostasis Governing Pathways in Alzheimer's Disease, Aging Cell, 17(5), e12801, 2018
- Yanpeng Ci, Xiaoning Li, Maorong Chen, Jiateng Zhong, Brian J. North, Hiroyuki Inuzuka, Xi He, Yu Li, Jianping Guo, and Xiangpeng Dai. SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation, Protein & Cell, 9, 879-889, 2018
- Ji Cheng, Jianping Guo, Zhiwei Wang, Brian J. North, Kaixiong Tao, Xiangpeng Dai, and Wenyi Wei. Functional analysis of Cullin 3 E3 ligases in tumorigenesis, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1869, 11-28, 2018
- Jianping Guo, Ji Cheng, Brian J. North, and Wenyi Wei. Functional analysis of major cancer-related signaling pathways in Alzheimer’s disease etiology, Biochimica et Biophysica Acta, 1868, 341-358, 2017
- Yuyong Tan, Yanpeng Ci, Xiangpeng Dai, Wenjian Gan, Fei Wu, Jianping Guo, Deliang Liu, Brian J. North#, Jirong Huo#, and Jinfang Zhang#. Cullin 3SPOP ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6, Oncotarget, 8, 47890-47901, 2017
- Bin Wang, Zuliang Jie, Donghyun Joo, Alban Ordureau, Pengda Liu, Jianping Guo, Wenjian Gan, Jinfang Zhang, Xiangpeng Dai, Brian J. North, Yuhan Chen, Xuhong Cheng, Xiuwu Bian, Lingqiang Zhang, J. Wade Harper, Shao-Cong Sun, and Wenyi Wei. TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling, Nature, 545, 365-369, 2017
- Brian J. North, Ingrid Almeciga-Pinto, David Tamang, Min Yang, Simon S. Jones, and Steven N. Quayle. Enhancement of pomalidomide anti-tumor response with ACY-241, a selective HDAC6 inhibitor, PLoS One, 12, e0173507, 2017
- Naoe Taira Nihira, Kohei Ogura, Kouhei Shimizu, Brian J. North, Jinfang Zhang, Daming Gao, Hiroyuki Inuzuka, and Wenyi Wei. Acetylation-dependent regulation of Mdm2 oncogenic function, Science Signaling, 10, 466, eaai8026, 2017
- Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C. Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J. North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seria Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M. Asara, Satoshi Fukumoto, Keiichi I. Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, and Wenyi Wei. The SCFbeta-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis., Science Signaling, 10, 460, eaah4117, 2017
Research and Scholarship Interests
- Molecular basis for aging and its impact on age-related disease susceptibility; Understanding the roles of E3 ubiquitin ligases in tumorigenesis; Regulation and function of NAD+-dependent deacetylases
Current Research Projects
- Aging is the single greatest risk factor for development of a wide variety of disease, yet the mechanistic basis driving this interrelationship remains largely undefined. BubR1, a serine/threonine protein kinase, is mutated in the rare human disease Mosaic Variegated Aneuploidy, which is highlighted by developmental defects, premature aging, and increased cancer incidence. BubR1 is involved in the spindle assembly checkpoint to ensure faithful chromosome segregation during mitosis, and therefore is intimately linked to aneuploidy and cancer. Intriguingly, a number of recent studies have implicated BubR1 in the aging process where BubR1 abundance has been shown to decline in a variety of tissues as mammals age. Previously, we identified an acetylation-dependent mechanism regulating BubR1 protein stability, where the deacetylase SIRT2 prevents degradation of BubR1 through maintaining BubR1 in a deacetylated state. Furthermore, reduced BubR1 protein levels in aged animals can be restored by stimulating SIRT2 activity through induction of NAD+ levels. These results suggest that the decline in BubR1 levels with age can be reversed, potentially alleviating age-related diseases including cancer. Therefore, we are interested in defining the detailed molecular mechanisms by which BubR1 declines with age which we anticipate will provide a greater understanding of the mechanisms driving both the process of aging as well as the establishment of age-related diseases. Furthermore, understanding the signaling pathways leading to BubR1 loss with age will provide impetus to target these pathways pharmacologically as treatments for cancer and other age-related diseases.
Grant Funding Received
- Nebraska Health and Human Services, Cancer and Smoking Disease Research Program - LB595 Program Project Grant. Title: Cellular Pathways Targeting BubR1 to the Proteasome for Degradation: Implications for Skin Cancer
- National Institute of Aging/NIH K01 grant (AG052627) Title: Mechanisms Controlling BubR1 Regulation of Cancer and Aging
- Creighton University Health Science Strategic Investment Fund Faculty Development grant Title: Regulation of the Cardiac Conduction System by BubR1