Dr. rer. nat.
Biochemistry and Molecular Biology
I graduated from University of Freiburg, Germany with a Diplom Degree (Master's Degree) in Biology. At Universities of Heidelberg and Freiburg, Germany I obtained a Ph.D. in the Department of Biology with Professor Dr. Albrecht Sippel, where I studied the genomic structure and alternative splicing of nuclear factor genes that regulate transcription of lysozyme gene.
I undertook postdoctoral training with Gregory Germino, M.D. at the Johns Hopkins University School of Medicine to study the genetics of human polycystic kidney disease (PKD). I carried out several seminal studies in the PKD field, including the initial sequencing effort of PKD1 (the principal PKD gene), establishing molecular interactions between the two major PKD gene products, polycystin-1 and polycystin-2, and discovering the "two-hit" mechanism for kidney cyst formation in human PKD1.
I joined the Johns Hopkins University School of Medicine as an Assistant Professor in 2002, and investigated as PI PKD protein processing and regulation in projects funded by two NIDDK R01s. My laboratory was the first to show and document the mechanism and significance of polycystin-1 cleavage at the G-protein coupled proteolytic site (GPS) for proper kidney and liver structure and function.
I joined University of Maryland School of Medicine/Nephrology as an Associate Professor in 2012. Work in the lab is supported by the NIDDK through an R01 and P30.
Polycystic kidney disease (PKD) is a group of inherited diseases characterized by dilatation of the tubular units of the kidney. The kidney tubules normally process the 140 liters of fluid filtered by the glomerulus into the final urine volume (0.5-2.0 liters) every day. Cystic tubules are unable to perform this function properly, resulting in fluid retention and kidney failure requiring dialysis or transplantation. PKD research has not only a great impact on human kidney disease, but can also shed critical insights into the fundamental mechanisms that control the polarity of tubular epithelial cells and the diameter of a tubule structure.
Research in my laboratory examines the molecular mechanisms of processing and trafficking of PKD proteins (polycystin-1, polycystin-2, and polyductin). We seek to elucidate the normal PKD signaling pathways and to understand the cellular pathways that are altered when the respective PKD genes are mutated, using a combination of biochemical, biophysical, cell biological methods and animal models.
|A surgically removed human PKD kidney
We focus on role of the cis-autoproteolytic cleavage of polycystin-1 at the GPS domain for its biological function. This fundamental property of polycystin-1 is absolutely essential for proper structure and function of kidney and liver. Pkd1 knock-in mouse with defective cleavage at GPS develops severe cystic dilation at the distal portion of the nephron at the postnatal period.
Cleavage is developmentally regulated in the kidney and generates various polycystin-1 forms likely to serve distinct functions for normal kidney development and maintenance. Our studies suggest that the full-length form serves a significant function for embryonic kidney development and survival in utero, while the GPS cleaved polycystin-1 products are required for normal distal tubular structure at postnatal stage. One hypothesis we are pursuing is that the full-length form of polycystin-1 plays a significant role in regulating the convergent extension process during nephrogenesis. Another ongoing project is to elucidate the molecular mechanism by which polycystin-1 GPS cleavage regulates ciliary targeting of polycystin-1 and polycystin-2 proteins. Another area of interest is the biology of autosomal recessive form of PKD, a disease caused by mutation in PKHD1. We are elucidating the genetic and molecular basis of the interaction between PKD1 and PKHD1.
Refereed Journal Articles (selected)
- Qian F*, Watnick TJ*, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell. 1996 Dec 13;87(6):979-87. (* Co-first author)
- Qian F, Germino 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.
- Watnick TJ, Torres VE, Gandolph MA, Qian F, Onuchic LF, Klinger KW, Landes G, Germino GG. Somatic mutation in individual liver cysts supports a two hit model of cystogenesis in autosomal dominant polycystic kidney disease, type I. Mol Cell. 1998 Aug;2(2):247-51.
- Reynolds DM, Hayashi T, Cai Y, Veldhuisen B, Watnick TJ, Lens XM, Mochizuki T, Qian F, Fossdal R, Coto E, Wu G, Breuning MH, Germino GG, Peters DJM, Somlo S. Abberant splicing in the PKD2 gene as a cause of polycystic kidney disease. J Am Soc Nephrol. 1999 Nov;10(11):2342-51.
- 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.
- 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, Bragonzi A, Cortese M, Courtoy PJ, Deen PM, Soria MR, Devuyst O, Monaco L, Germino GG. Biochemical characterization of bona fide polycystin-1 in vitro and in vivo. Am J Kidney Dis. 2001 Dec;38(6):1421-9.
- Chauvet V, Qian F, Boute N, Cai Y, Phakdeekitacharoen B, Onuchic LF, Attie-Bitach T, Guicharnaud L, Devuyst O, Germino GG, Gubler MC. Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development. Am J Pathol. 2002 Mar;160(3):973-83.
- Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu PN, Germino FJ, Germino GG. PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell. 2002 Apr 19;109(2):157-68.
- 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 USA. 2002 Dec 24;99(26):16981-6.
- Piontek KB., Huso DL., Grinberg A., Liu L., Bedja D., Zhao H., Gabrielson K., Qian F., Mei C., Westphal H., and Germino GG. A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo. J Am Soc Nephrol. 2004 Dec;15(12):3035-43.
- Hackmann K., Markoff A., Qian F., Bogdanova N., Germino GG., Pennekamp P., Dworniczak B., Horst J., Gerke V. A splice form of polycystin-2, lacking exon 7, does not interact with polycystin-1. Hum Mol Genet. 2005 Nov 1;14(21):3249-62.
- 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. Epub 2005 Oct 11.
- Li Y., Wright JM., Qian F., Germino GG., Guggino WB. Polycystin 2 interacts with type I inositol 1,4,5- trisphosphate receptor to modulate intracellular Ca2+ signaling. J Biol Chem. 2005 Dec 16;280(50):41298-306.
- Boca M., Distefano G., Qian F., Bhunia AK., Germino GG., Boletta A. Polycystin-1 Induces Resistance to Apoptosis through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway. J Am Soc Nephrol. 2006 Mar;17(3):637-47.
- Wei W., Hackmann K., Xu H., Germino GG., and Qian 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.
- 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.
- Wodarczyk C., Rowe I., Chiaravalli M., Pema M., Qian F., Boletta A. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus. PLoS One. 2009 Sep 23;4(9):e7137.
- Li Y., Santoso NG., Yu S., Woodward OM., Qian F., Guggino WB. Polycystin-1 interacts with IP3R to modulate intracellular Ca2+ signaling, with implications for polycystic kidney disease. J Biol Chem. 2009 Dec 25;284(52):36431-41.
- Woodward OM., Li Y., Yu S., Greenwell P., Wodarczyk C., Boletta A., 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.
- Schroder S., Fraternali F., Quan X., Scott DJ., Qian F., Pfuhl M. "When a module is not a domain - the case of the REJ module and the redefinition of the architecture of polycystin". Biochem J. 2011 May 1;435(3):651-60.
- Steigelman KA, Lelli A, Wu X, Gao J, Lin S, Piontek K, Wodarczyk C, Boletta A, Kim H, Qian F, Germino G, Géléoc GS, Holt JR, Zuo J. "Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells" J Neurosci. 2011 Aug 24;31(34):12241-50.
- Foy RL, Chitalia VC, Panchenko MV, Zeng L, Lopez D, Lee JW, Rana SV, Boletta A, Qian F, Tsiokas L, Piontek KB, Germino GG, Zhou MI, Cohen HT. "Polycystin-1 regulates the stability and ubiquitination of transcription factor Jade-1." Hum Mol Genet. 2012 Sep 21.
- 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. (* Qian corresponding author)
- 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. (Qian corresponding author)
- Qian F., Germino GG. Electrophoresis of DNA and RNA Fragments, in Techniques in Molecular Medicine, Edited by Hildebrandt F and Igarashi P, Springer-Verlag, pp. 71-81, 1999.
- Qian F., Germino GG. Single-Strand Conformation Polymorphism (SSCP) Analysis, in Techniques in Molecular Medicine, Edited by Hildebrandt F and Igarashi P, Springer-Verlag, pp. 82-85, 1999.
- Qian F., Germino GG. Introduction of Pulsed-Field Gel Electrophoresis (PFGE), in Techniques in Molecular Medicine, Edited by Hildebrandt F and Igarashi P, Springer-Verlag, pp. 96-102, 1999.
- Qian F. Polycystin-1. Handbook of Proteolytic Enzymes 3rd Edition, Elsevier, Oxford, UK, in press.