Sun Laboratory

Dandan Sun, MD, PhD

Dandan Sun, MD, PhD

Professor, Endowed chair of Brain Disorders Research
E-mail Website

Interests

The proper regulation of ionic homeostasis is critical for maintaining cellular function of the brain. The Sun laboratory is interested in the role of ion transporters in different neurological disorder models of neuropathology. We primarily focus on the Na-K-Cl cotransporter protein NKCC1 and the Na/H exchanger protein NHE1. There are 3 ongoing projects:

➢ Role of the WNK-SPAK/OSR1-NKCC1 signaling cascade in ischemia-induced brain damage. NKCC1 mediates Na+ and Cl- influx and is involved in cerebral edema and ischemic brain damage. We use transgenic knockout approaches or drugs that inhibit parts of this pathway to evaluate their potentials as therapeutic targets to prevent or treat ischemic stroke.

➢ Ion transporters in neuropathology of glioblastoma multiforme (GBM).
Our research has demonstrated the role of ion transporters in regulating Cl- influx, cell volume, and intracellular pH, which impact GBM cancer cell survival and migration. We are now exploring the microglia-glioma signaling mechanisms regulated by ion transporters that determine glioma cell invasiveness. These ion transporters and their underlying signaling mechanisms may be potential targets for therapeutic interventions to treat GBM.

➢ Role of endoplasmic reticulum (ER) stress in the neuropathology after traumatic brain injury (TBI). The ER is an important organelle responsible for maintaining the cellular homeostasis. Disturbances in Ca2+ signaling and the normal functions of the ER lead to a cell stress response, which eventually triggers cell death. We have demonstrated that a sustained ER stress response correlates with neurological deficits after TBI. Most importantly, docosahexaenoic acid (DHA), an important component of fish oil, has protective effects in reducing ER stress. We are investigating the molecular mechanisms that convey neuroprotection after inhibition of ER stress.

Our research is conducted using in vitro and in vivo models with a variety of biochemical assays and live cell imaging techniques. Student internship positions are available for dedicated, well qualified students.

Training

MD Medicine Harbin Medical University 1983
PhD Physiology University of Wisconsin-Madison 1992

Positions Held

Tenure-track Assistant Professor University of Wisconsin-Madison 1997-2002
Associate Professor University of Wisconsin-Madison 2002-2006
Professor University of Wisconsin-Madison 2007-2011
Professor, Endowed Chair of Brain Disorders Research University of Pittsburgh School of Medicine 2011-present

Honors and awards

1994-1997 Postdoctoral Fellowship of NIH Training Program in Cardiovascular and Neurophysiology at the University of California-Davis
1997-2000 Scientist Development Grant from the American Heart Association National Center
1998-2000 Faculty Development Grant from University of Wisconsin Medical School under the
1998-2001 Howard Hughes Medical Institute Research Resources Program for Medical School
2000-2004 CAREER grant from the National Science Foundation
2005-2009 Established-Investigator Award from American Heart Association (AHA)
2000-2008 Hilldale Undergraduate/Faculty Research Awards at UW-Madison
2012-2015 Faculty Sponsor for Brackenridge Undergraduate Research Fellowship at Univ. Pitt
2014 Faculty Sponsor for Chancellor’s Undergraduate Research Fellowship at Univ. Pitt
2010-2014 Chair of Brain 3, AHA National Innovative Research Grant (IRG) study section
2013-2019 NIH ZRG1 CMBG study section, regular member
2015-present AHA Peer Review Committee member, Brain 3
2015-present Dept. of Veterans Affairs DVA Review Committee member (Neurobiology C)

Selected Publications

➢ Begum G, Yuan H, Kahle KT, Li L, Wang S, Shi Y, Shmukler BE, Yang SS, Lin SH, Alper SL, Sun D. Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and Accelerates Neurological Recovery After Stroke. Stroke, 46(7):1956-65, 2015.
Link: http://stroke.ahajournals.org/content/46/7/1956.full.pdf+html

➢ Cong D, Zhu W, Shi Y, Pointer KB, Clark PA, Shen H, Kuo JS, Hu S, Sun D. Upregulation of NHE1 protein expression enables glioblastoma to escape TMZ-mediated toxicity via increased H+ extrusion, cell migration and survival. Carcinogenesis, 35(9):2014-24, 2014.
Link: http://carcin.oxfordjournals.org/content/35/9/2014.full.pdf+html

➢ Begum G, Yan HQ, Li L, Singh A, Dixon CE, Sun D. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury. Journal of Neuroscience, 34(10):3743-55, 2014.
Link: http://www.jneurosci.org/content/34/10/3743.full.pdf+html

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