Shirley ShiDu Yan

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


Research conducted in Dr. Yan’s laboratory is geared toward unraveling the cellular and molecular basis of neurodegeneration and devising therapeutic strategies to hamper the processes that cause neuronal death.

Research

Dr. 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. Dr. Yan and her research team are the major group investigating these paradigms. Dr. 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. Dr. 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, Dr. 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 review, Dr. Yan 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. Dr. 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.

Dr. 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.

I have 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. I am 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
KU Today
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 needy Kansans 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