[et_pb_section fullwidth=”on” specialty=”off”][et_pb_fullwidth_slider admin_label=”Fullwidth Slider” show_arrows=”on” show_pagination=”on” auto=”off” parallax=”off” parallax_method=”off” module_id=”interior”][et_pb_slide background_image=”https:\/\/depts.washington.edu\/cfrtc\/wp-content\/uploads\/2014\/12\/microscope.jpg” background_color=”#ffffff” alignment=”center” background_layout=”dark” \/][\/et_pb_fullwidth_slider][\/et_pb_section][et_pb_section][et_pb_row][et_pb_column type=”1_4″][et_pb_sidebar admin_label=”Fellowships Sidebar” orientation=”left” area=”et_pb_widget_area_11″ background_layout=”light” \/][\/et_pb_column][et_pb_column type=”3_4″][et_pb_text admin_label=”Current Fellow Bellairs” background_layout=”light” text_orientation=”left”]<\/p>\n
Fellow: Magdalena Donczew, PhD<\/a> Mentor: David Sherman, PhD<\/a> Pulmonary infections with Mycobacterium abscessus complex (MABSC) are one of the most challenging to treat, with an average treatment success rate of 46%. The main aim of the proposed project is to investigate why there is a large discrepancy between MABS drug susceptibility measured in vitro and patient response to therapy and to identify the mechanism through which MABSC develops drug tolerance. I hypothesize that MABS intrinsic resistance to multiple antibiotic classes results mostly from its heterogenous phenotypes and complex interplay between MABS and other cystic fibrosis (CF) pathogens. I also hypothesize that there are important genetic differences between mycobacterial strains that control phenotypic heterogeneity and lead to clinically relevant variations between strains.<\/p>\n I propose to test these hypotheses by combining our advances in time lapse microscopy with comparative genome analysis. I will apply ODELAM (One-cell Doubling Evaluation by Living Arrays of Mycobacteria), a novel time-lapse microscopy platform, to evaluate the effects of antibiotic(s) and interspecies interactions on the phenotypic heterogeneity of different clinical MABS strains. Because of the utilization of MABS strains with known treatment outcome I plan to characterize the relevance of the phenotypic heterogeneity in mycobacterial treatment response and risk of disease relapse. By integrating phenotypic heterogeneity characteristics and analysis of genomic sequences of a set of MABS strains, I will identify candidate genes that promote or impede mycobacterial heterogeneity. Predicted genes will be further verified through targeted deletions followed by characterization of heterogeneity.<\/p>\n The results of this project will substantially advance our understanding of the mechanisms by which MABS adopts to drugs and provide insights into new drug targets and strategies that will help to improve current treatment approaches for difficult CF infections.<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" Fellow: Magdalena Donczew, PhD Mentor: \u00a0David Sherman, PhD P.I.: Ian de boer, MD<\/a>
\nMicrobiology<\/p>\n
\nProfessor and Chair, Microbibology<\/p>\n
\nMicrobiology<\/p>\n
\nProfessor and Chair, Microbiology<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"
Associate Professor of Medicine
Nephrology<\/p>