Shirley ShiDu Yan

  • Howard E. Mossberg Distinguished Professor
  • School of Pharmacy - Pharmacology & Toxicology
785-864-3637
Office
Smissman Research Laboratories, Room 164
University of Kansas
2099 Constant Avenue
Lawrence. KS, 66047-2535

Education

  • Post Doc, Physicians & Surgeons College of Columbia University, New York, NY (1993)
  • M.D., Fujian Medical University,Fuzhou Shi, Fujian Sheng, China (1983)

Biography

Shirley Yan’s research is geared toward unraveling the cellular and molecular basis of neurodegeneration and devising therapeutic strategies to hamper the processes that cause neuronal death. Yan’s Lab was the first to identify the specific cellular targets (RAGE, receptor for advanced glycation end product; ABAD, amyloid binding alcohol dehydrogenase, and cyclophilin D) of amyloid-beta peptide (Aβ) and to find evidence of Aβ-mediated neuronal stress. We have developed a novel transgenic mouse model relevant to the pathogenesis of neurodegenerative diseases including Alzheimer disease (AD), multiple sclerosis, and Parkinson disease. Through analyses of genetically manipulated AD-type mouse models, we have elucidated new insights into cellular and molecular mechanisms underlying the pathogenesis of AD. All of our findings indicate that cell surface RAGE and intracellular proteins such as ABAD or cyclophilin D service as cellular co-factors for promoting Aß-mediated neuronal toxicity relevant to Alzheimer’s disease. In the future, we may blockade these targeted proteins as a novel therapeutic approach in the treatment of Alzheimer’s disease.

Mitochondrial dysfunction is a hallmark of AD. Following up on their studies, Yan and her research team were the first to find that Aβ progressively accumulates in the mitochondria of brains from AD patients and transgenic AD-type mouse model. Accumulation of Aβ in mitochondria was associated with mitochondrial dysfunction. The interaction of mitochondrial Aβ with its binding protein exaggerates mitochondrial and synaptic dysfunction. These studies provide new insights into mechanisms of Aβ-mediated mitochondrial toxicity causing neuronal damage relevant to AD and open new avenues for the treatment of AD. Recently, Yan’s group has provided substantial evidence of mitochondrial abnormalities directly linked to synaptic dysfunction. These studies have been highlighted in globally leading journals including Nature, Nature Medicine, Science, and PNAS. Yan’s research has been supported by the grant from the National Institutes of Health and other foundations since 1995. Yan’s research clearly advances our understanding of mechanisms through which Aβ induces cellular stress. Her work could lead to new therapeutic strategies for AD.

Yan also has expertise in cellular and molecular mechanisms of ischemia-induced cardiac and cerebral injury, autoimmune disease such as EAE (experimental autoimmune encephalomyelitis) animal model relevant to multiple sclerosis, and Parkinson disease. Recently, we are working on a project related to tumor pathogenesis. She has been a keynote speaker at multiple international professional scientific meetings. She is an active member of multiple scientific review committees for neurodegenerative disease of the National Institutes of Health (NIH), VA merit grant, Alzheimer Association, and other foundation grants. Yan’s laboratory has been collaborating with research scientists from Japan, Germany, Italy, and England, in addition to the United States.

Research Overview

Shirley Yan’s research focuses on investigating the cellular and molecular mechanisms of cellular stress and survival in neurodegenerative disorders relevant to Alzheimer’s disease (AD) and Parkinson disease. She has first identified the specific cellular targets (RAGE, receptor for advanced glycation end product; and ABAD, amyloid binding alcohol dehydrogenase) of amyloid-beta peptide (Aβ) and found the evidence of Aβ-mediated neuronal stress. She developed a novel transgenic mouse model relevant to AD and tested the role of RAGE and ABAD in Aβ-mediated cellular perturbation in those AD type mouse models. She was the first to describe the RAGE and ABAD as the functional binding proteins for Aβ. Yan and her research team are the major group investigating these paradigms. Yan and her research team have provided evidence that cell surface molecule (RAGE) and mitochondrial enzyme (ABAD) serve as cofactors for promoting and exaggerating neuronal and mitochondrial toxicity in an Aβ-rich environment.

Mitochondrial dysfunction is a hallmark of AD. Yan and her research team have followed up their studies and first found that Aβ progressively accumulated in mitochondria of brains from AD patients and transgenic AD-type mouse model. Accumulation of Aβ in mitochondria was associated with mitochondrial dysfunction. ABAD directly linked to mitochondrial toxicity induced by Aβ. These studies provide new insights into mechanisms of Aβ-mediated mitochondrial toxicity causing neuronal damage relevant to AD and open new avenue for treatment of AD. Recently, Yan’s group have provided substantial evidence of mitochondrial abnormalities directly link to the synaptic dysfunction which is an early feature in the AD pathogenesis. These studies open new avenue for therapeutic strategy of AD. As stated by the committee of my NIH grant reviewYan is a pioneer in the studies RAGE/ABAD and their roles in an Aβ-induced mitochondrial and neuronal perturbation of AD. She is a highly regarded and world-wide leader in the field of AD neuropathogenesis and has made very important contributions to the AD field. Her research projects are very innovative. Yan and her research team are the major group investigating these paradigms (RAGE/ABAD, mitochondria and pathogenesis of AD).

These studies have been highlighted in world-wide leading Journals including Nature (2 papers), Nature Medicine (10 papers), Science, PNAS, and other professional leading Journals. The paper on CypD (Du et al., Nature Medicine, 2008) was ranking top#3 of hot papers in Alzheimer's disease research in year 2008-2010 (http://www.timeshighereducation.co.uk/story.asp?sectioncode=26&storycode...). She is a keynote speaker at multiple international professional scientific meetings and member of scientific review committee. Her research projects are continuously supported by NIH. She has received grant award from NIA [Program Project Grant since 2000, a total of $14 million for 10 years period (07/01/2000-06/30/2012)] to continually support her research on aging and Alzheimer’s disease. Her work clearly advances our understanding of mechanisms through which Aβ induces cellular stress and moves AD field forward. Her work could lead to new therapeutic strategies for AD. In addition, results generated from our studies have been patented or filed for the patent applications. RAGE antagonists are in the clinical trial (phase II). Based on her exceptional outstanding research and track record of publication, she has recently received extraordinary MERIT (Method to Extend Research in Time) award (R37) from NIA. MERIT award is one of the most prestigious awards presented by the NIH and provide long-term support to exceptional outstanding and experienced investigators who contributes significantly to the research field. MERIT awards enable scientists who have impressive track records of scholarship and productivity to have long-term sustained funding without the time and effort of seeking competitive grant renewal.

Research conducted in my laboratory is geared toward unraveling the cellular and molecular basis of neurodegeneration and devising therapeutic strategies to hamper the processes that cause neuronal death. To this end, we have focused our research efforts on the transgenic animal model of Alzheimer’s disease. We have developed a novel transgenic mouse model relevant to the pathogenesis of AD, such as transgenic mice expressing both mutant form of human APP and RAGE or ABAD targeted to neurons, smooth muscle cells, endothelial cells, respectively, and deletion of ABAD gene. Those novel transgenic AD-type mouse models greatly benefit the scientific AD communities. Some of these transgenic mouse models have been listed in the Double-cross research models of Alzheimer Research Forum (http://www.alzforum.org/res/com/tra/double-cross/default.asp).Through analyses of genetically manipulated AD-type mouse models, we have elucidated new insight into cellular and molecular mechanisms underlying the pathogenesis of AD.

Yan also has an expertise on cellular and molecular mechanisms of ischemia-induced cardiac and cerebral injury, autoimmune disease such as EAE (experimental autoimmune encephalomyelitis) animal model relevant to multiple sclerosis, and Parkinson’s disease. Those studies are supported by NIH and other foundation grants.

She received the Zenith Fellow Award from the Alzheimer’s Association in 2005. The Zenith Fellow Award only gives an established independent investigator who has contributed significantly to the field of Alzheimer’s disease research. She is an active member of multiple scientific review committees for neurodegenerative disease of National Institute of Health (NIH), VA merit grant, and other foundation grants.

Her Laboratory has been collaborating with research scientists from Japan, Germany, Italy, Saudi Arabia, and United Kingdom, in addition to United States.


Events
2nd among all schools of pharmacy in National Institutes of Health funding
Brings more than $20 million in external funding into the state each year
7 of 19 cancer drugs formulated through the National Cancer Institute were developed at the KU School of Pharmacy
3,000 free flu shots given to Kansans in need during the past 5 years
4,000 living alumni, 63 percent of them living and working in Kansas
KU pharmacists practice in 95 of Kansas’ 105 counties
20th among public schools of pharmacy.
—U.S. News & World Report
$20.2 million NIH research grant earned by Distinguished Professor Jeff Aubé was 2nd largest in Kansas history
100 percent placement after graduation for KU Pharm.D. students
Established in 1885 as the 1st professional program at KU