Research Faculty

Qingxian Lu, Ph.D.

Assistant Professor, Department of Ophthalmology and Visual Sciences

CONTACT INFORMATION:

301 E. Muhammad Ali Boulevard, Louisville KY 40202
Telephone : (502)-852-4768 Fax : (502)-852-4595
E-mail: q.lu@louisville.edu

EDUCATION:

RESEARCH INTERESTS:

My research interests are focused on elucidating molecular mechanisms of three closely-related receptor tyrosine kinases, called Tyro3, Axl and Mertk (TAM), in regulation of phagocytic activity in professional and non-professional phagocytes, particularly in the retinal pigmental epithelium cells in the eye. Phagocytic clearance of the spent photoreceptor distal outer segment (OS) tips by the retinal pigmental epithelium (RPE) cells is essential to maintain photoreceptor homeostasis. Failure of RPE phagocytosis of the OS leads to retinitis pigmentosa (RP). Mutation in the Mertk receptor tyrosine kinase causes photoreceptor degeneration. To understand the molecular role of Mertk in phagocytosis, we have used Mertk mutated RPE cells as a model to identify Mertk downstream target genes or signaling molecules that are involved in regulation of the phagocytic events. Gene expression pattern and signaling pathways are studied in the primary cultured RPE cells and the difference between wild-type and Mertk mutant is carefully compared. The candidate target genes or signaling molecules are intentionally up- or down-regulated in RPE cells to test their effects on the phagocytic activity.

In addition, degenerating retina in the mutants generates rich apoptotic materials accumulating neo-epitopes that are captured and processed by antigen-presenting cells (APC) and subsequently presented to helper T cells, as a result, the mutant mice produce elevated retinal autoantibodies and increased retinal antigen-specific T cells. TAM receptors play a negative regulatory role in APC to prevent over production of proinflammatory cytokines in responses to pathogen infection. Taken advantage of current knowledge on the functional role of TAM receptors in APCs, we have set out to investigate how TAM receptors influence APC responses to retinal autoantigens and what are the molecular mechanisms underlying the development of ocular autoimmunity.

PUBLICATIONS:

1. Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagranda F, Lai C, Skinner MK, Klein R, Matsushima GK, Earp HS, Goff SP, Lemke G. Tyro 3 family receptors are essential regulators of mammalian spermatogenesis. Nature. 1999 Apr 22;398(6729):723-8. PMID: 10227296
2. Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001 Jul 13;293(5528):306-11. PMID: 11452127
3. Prasad D, Rothlin CV, Burrola P, Burstyn-Cohen T, Lu Q, Garcia de Frutos P, Lemke G. TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci. 2006 Sep;33(1):96-108. Epub 2006 Aug 9. PMID: 16901715
4. Caraux A, Lu Q, Fernandez N, Riou S, Di Santo JP, Raulet DH, Lemke G, Roth C. Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases. Nat Immunol. 2006 Jul;7(7):747-54. Epub 2006 Jun 4. PMID: 16751775
5. Xiong W, Chen Y, Wang H, Wang H, Wu H, Lu Q, Han D. Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction. 2008 Jan;135(1):77-87. PMID: 18159085
6. Zheng Y, Zhang L, Lu Q, Wang X, Yu F, Wang X, Lu Q. NGF-induced Tyro3 and Axl function as survival factors for differentiating PC12 Cells. Biochem Biophys Res Commun. 2009 Jan 16;378(3):371-5. Epub 2008 Nov 24. PMID: 19027714.