Benutzerspezifische Werkzeuge

Cell Biology Unit

KFO252_long

Cell Biology Unit

Head: Nan Qin, PhD
Catleen Conrad (Technical assistant)

Research carried out in the Cell Biology unit under Dr. Nan Qin is focused on untangling the signaling networks involved in development and transformation of tumors with a specific focus on the links between hypoxia and MYC-associated pathways. Such pathways are central not only to development of many neoplasms, but also to processes of differentiation, which can provide insights into stem cell biology with relevance to regenerative therapies.

Dr. Qin’s research takes advantage of the Division’s well-established background of research into chromaffin cell tumors. With now in excess of 16 mutated genes identified as responsible for pheochromocytomas and paragangliomas, these tumors have one of the richest genetic backgrounds among all neoplasms. This provides advantages to studies directed at unraveling tumorigenic pathways. Using genomic-directed bioinformatic processing of transcriptome profiles from the Divisions extensive banks of human tumor specimens, Dr. Qin investigates pathways downstream of mutated genes. Cell biological studies involve model systems engineered with insertions or deletions of genes of interest, with use of CRISPR/Cas9 technology now enabling precise and efficient gene editing. Functional consequences of altered gene function and alterations of transcriptome profiles in cell model systems are examined and compared with mutation-associates differences in clinical presentation and transcriptome profiles of tumors in affected patients. Using this approach Dr. Qin has identified a hypoxia-linked MYC/MAX pathway that determines distinct phenotypic differences according to underlying mutations as well as differences in behavior of tumors. Importantly, this pathway provides an upstream link to almost all identified mutations responsible for chromaffin cell tumors.

HIF_MYC_pathway

Using protein complex chromatin immunoprecipitation (ChIP) followed by deep sequencing, Dr. Qin is now moving forward to establish the precise binding partners, mechanisms and downstream targets of this central pathway of tumorigenesis. Defining this pathway has long-range potential not only for therapies directed at metastatic neoplasms arising from the neural crest but also other neoplasms for which this and related pathways might be important. 

 

Selected Publications

  1. Vukićević V, Qin N, Balyura M, Eisenhofer G, Wong ML, Bornstein SR and Ehrhart-Bornstein M.. Valproic acid enhances neuronal differentiation of sympathoadrenal progenitor cells. Mol Psychiat,ry 2015 “in press’’
  2. Qin N, de Cubas AA, Garcia-Martin R, Richter S, Peitzsch M, Menschikowski M, Lenders JW, Timmers HJ, Mannelli M, Opocher G, Economopoulou M, Siegert G, Chavakis T, Pacak K, Robledo M, Eisenhofer G. Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC-associated factor X. Int J Cancer. 2014;135:2054-64.
  3. Ullrich M, Bergmann R, Peitzsch M, Cartellieri M, Qin N, Ehrhart-Bornstein M, Block NL, Schally AV, Pietzsch J, Eisenhofer G, Bornstein SR, Ziegler CG. In vivo fluorescence imaging and urinary monoamines as surrogate biomarkers of disease progression in a mouse model of pheochromocytoma. Endocrinology. 2014,155: 4149-56.
  4. Qin N, Peitzsch M, Menschikowski M, Siegert G, Pacak K, & Eisenhofer G. Double stable isotope ultra performance liquid chromatographic-tandem mass spectrometric quantification of tissue content and activity of phenylethanolamine N-methyltransferase, the crucial enzyme responsible for synthesis of epinephrine. Anal Bioanal Chem 2013;405:1713-1719.
  5. Burnichon N, Cascón A, … Qin N, …. Eisenhofer G, Gimenez-Roqueplo AP, Robledo M. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res. 2012,18: 2828-37.