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Feng Qian, Dr. rer. nat.

Academic Title:

Associate Professor

Primary Appointment:

Medicine

Secondary Appointment(s):

BioChemistry&Molecular Biology

Location:

BRB, 2-17A

Phone (Primary):

410-706-5804

Education and Training

I received undergradaute education in biology from University Giessen, Germany and obtained my Diplom Degree (Master's Degree) in Biology from University of Freiburg, Germany. I received my Ph.D. from the Universities of Heidelberg and Freiburg, Germany in 1993 under the supervision of Professor Dr. Albrecht Sippel. I then pursued postdoctoral training in the laboratory of Stephen Reeders, M.D. (Yale Univesity School of Medicine) in 1993, followed by a fellowship with Gregory Germino, M.D. (the Johns Hopkins University School of Medicine) from 1993-1996 to study polycystic kidney disease (PKD). I joined the Johns Hopkins University School of Medicine as an Assistant Professor in 2002, and joined University of Maryland School of Medicine as an Associate Professor in 2012. 

Biosketch

A major goal of my laboratory is to understand the function of proteins encoded by genes (PKD1/polycystin-1, PKD2/polycystin-1 and PKHD1/polyductin) whose mutations result in human polycystic kidney disease (PKD). PKD is a group of inherited diseases characterized by massively enlarged kidneys (an example is shown in the figure below) with tubualr dilatation of the nephrons . A long-term goal is to understand fundamental mechanisms that control the polarity of tubular epithelial cells and the diameter of a tubule structure. A parallel aim is to understand how mutations result in the disease phenotype. Our ultimate goal is to establish a firm mechanistic understanding of the disease process, which can ultimately be used to guide the rational development of therapies.

Removed PDK Kidney
A surgically removed human PKD kidney

 

Research/Clinical Keywords

Polycystic kidney disease, polycystin, cyst formation, ciliary trafficking, cis-autoproteolysis, G-protein coupled protein proteolysis site (GPS)

Highlighted Publications

Qian FGermino FJ, Cai Y, Zhang X, Somlo S, Germino GG. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat Genet. 1997 Jun;16(2):179-83. PMID: 9171830.

Qian F, Watnick TJ, Onuchic LF, Germino GG (1996).  The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I.  Cell, 87:979-987. PMID:8978603.

Qian F., Boletta A., Bhunia AK., Xu H., Liu L., Ahrabi AK., Watnick TJ., Zhou F., Germino GG. Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney 1-associated mutations. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16981-6. PMID: 12482949.

Yu S., Hackmann K., Gao J., Piontek K., García-González MA., Menezes LF., Xu H., He X., Germino GG., Zuo J., and Qian F. Essential role of proteolytic cleavage of polycystin-1 for kidney tubular structure. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18688-93. PMID:18003909.

Kurbegovic A, Kim H, Xu H, Yu S, Cruanès J, Maser RL, Boletta A, Trudel M, Qian F. “Novel functional complexity of polycystin-1 by GPS cleavage in vivo: role in polycystic kidney disease.” Mol Cell Biol. 2014 Sep;34(17):3341-53. PMID:24958103.

Kim HXu HYao QLi WHuang QOuteda PCebotaru VChiaravalli MBoletta APiontek KGermino GGWeinman EJWatnick T, and Qian F,“Ciliary membrane proteins traffic through the Golgi via a Rabep1/GGA1/Arl3-dependent mechanism”. Nat Commun. 2014 Nov 18;5:5482. PMID:25405894. 

Additional Publication Citations

Qian F, Kruse U, Lichter P, and Sippel AE.  Chromosomal localization of the four genes (NFIA, B, C, and X) for the human transcription factor nuclear factor I by FISH. Genomics. 1995 Jul 1;28(1):66-73.

The AMERICAN PKD1 consortium: Burn T.C., Connors T.D., Dackowiki WR., Petry, LR., Van Raay, TJ., Millholland JM., Venet M., Miller G., Hakim, RM., Landes GM., Klinger, KW., Qian F*., Onuchic, LF., Watnick T., Germino GG., Doggett NA.  Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. Hum Mol Genet. 1995 Apr;4(4):575-82 (*Qian is the lead author of the Johns Hopkins University team).

Qian F., Germino GG. "Mistakes Happen": Somatic Mutation and Disease. Am J Hum Genet. 1997 Nov;61(5):1000-5.

Qian F., Watnick TJ. Somatic mutation as mechanism for cyst formation in autosomal dominant polycystic kidney disease. Mol Genet Metab. 1999 Oct;68(2):237-42.

Hanaoka K, Qian F*, Boletta A, Bhunia A, Piontek K, Tsiokas L, Sukhatme VP, Germino GG, Guggino WB.  Co-assembly of polycystin 1 and 2 produces unique cation permeable currents. Nature. 2000 Dec 21-28;408(6815):990-4 (*Co-first author).

Boletta A, Qian F, Onuchic LF, Bhunia AK, Phakdeekitcharoen B, Hanaoka K, Guggino W, Monaco L, Germino GG.  Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Mol Cell. 2000 Nov;6(5):1267-73.

Qian F., Wei W., Germino GG., Oberhauser AF. The nanomechanics of polycystin-1 extracellular region. J Biol Chem. 2005 Dec 9;280(49):40723-30. PMID: 16219758

Qian F, Noben-Trauth K. Cellular and molecular function of mucolipins (TRPML)and polycystin 2 (TRPP2). Pflugers Arch-European Journal of Physiology. 2005 Oct;451(1):277-85. Epub 2005 Jun 22. 

Wei WHackmann KXu HGermino GQian F. Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene. J Biol Chem. 2007 Jul 27;282(30):21729-37. PMID: 17525154.

Woodward OM., Li Y., YuS., GreenwellP., WodarczykC., BolettaA., Guggino WB and Qian F. Identification of a Polycystin-1 cleavage product, P100, that regulates store operated Ca2+ entry through interactions with STIM1. PLoS One. 2010 Aug 23;5(8):e12305.

Qian F. Polycystin-1. Handbook of Proteolytic Enzymes 3rd Edition, Elsevier, Oxford, UK, 2013.

Qian F. The Role of GPS cleavage in Polycystin-1 Biogenesis, Trafficking and Function, in"Polycystic Kidney Disease".by Codon Publications, Australia. October 2015.

Trudel MYao QQian F. “The role of G-protein-coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kindey Disease."   Cells. 2016 Jan 21;5(1). pii: E3. PMID:26805887

Research Interests

Role of GPS cleavage in polycystin-1 biology and PKD - We have discovered that polycystin-1 is proteolytically cleaved at the juxamembrane G-protein coupled receptor proteolysis site (GPS) motif via a cis-autoproteolytic mechanism (left panel in the figure below). GPS cleavage is a defining feature of the newly-categorized adhesion-GPCRs, the second largest subgroup of GPCRs in human genome. In one series of projects we have established that this post-translational modification is essential for polycystin-1 in regulating proper structure and function of kidney and liver, and, when defective, causes PKD. Pkd1 knock-in mouse with defective GPS cleavage of polycystin-1 develops severe cystic dilation at distal nephron segments in the postnatal period (right panel of the figure). We use molecular biology, biochemistry, and cell biology techniques together with orthologous mouse models of PKD, to study how GPS cleavage regulates polycystin-1’s biogenesis, trafficking and function.

PKHD1/Polyductin in kidney physiology and PKD - Another area of interest is the function of polyductin protein (encoded by the third major PKD gene, PKHD1) in kidney physiology and PKD. Using genetic analysis with unique hypomorphic Pkhd1 and Pkd1 alleles in mice, we have found that the two major PKD loci interact in cystogenesis in the perinatal period and the two forms of PKD share some underlying pathogenic mechanisms during development. We employ a multidisciplinary approach (electron microscopy, biochemistry, proteomic and transcritptomic analyses) to develop a mechanistic understanding of the Pkhd1/Pkd1 interaction and to define points of convergence of the polyductin and polycystin-1 pathways in kidney physiology and PKD.

Awards and Affiliations

2001             Johns Hopkins University, Department of Medicine Basic Research

                        Junior Faculty Award

2001             National Kidney Foundation of Maryland Professional Development Award

2002             American Heart Association Scientist Development Award

2005             U.S. Patent No. 5,654,170: "Polycystic Kidney Disease Gene".

                        By Germino GG, Qian F and Integrated Genetics/Genzyme

Grants and Contracts

NIH/NIDDK P30DK090868      

Baltimore PKD Research and Clinical Core Center As Antibody and Vector Core Director, our goals are  to provide the national and international  research base investigators with polycystins and polyductin specific reagents (expression constructs, antibodies, and cell lines) and expertise.

 

Polycystic Kidney Disease Foundation         

"Role of fibrocystin/polyductin in health and ARPKD"

 

 NIH NIDDK   1R56 DK111611       

The Molecular Mechanisms of Polycystin-1 Proteolytic Cleavage in Kidney Health and Polycystic Kidney Disease