Michael Rauchman

MDCM, McGill University (Developmental Biology; Epithelial Cell Injury and Regeneration)

Department: Internal Medicine

Academic Rank: Assistant Professor

Phone: 314-977-9366 Fax: 314-977-9205

E-mail: rauchman@slu.edu

Lab Web Page Links: http://biochemweb.slu.edu/index.php?page=michael-rauchman

Primary Area of Cardiovascular Research Interest

-Transcriptional regulation of kidney and genitourinary tract development
-Role of developmental control genes in epithelial cell regeneration after acute kidney injury

Related Areas of Cardiovascular Research Interest

-Congenital anomalies of the kidney and heart in Townes-Brocks, Okihiro and Holt-Oram syndromes
-Biochemistry of Sall family transcription factors and their co-regulatory factors
-Genetic analysis of the nucleosome remodeling and deacetylase (NuRD) complex components in kidney development and disease

Summary of Cardiovascular Research Interest

Congenital anomalies of the urinary tract are among the most common serious birth defects. Impaired outgrowth and branching of the ureteric bud is a common developmental mechanism that leads to renal hypoplasia (small kidneys) or agenesis (no kidneys form). These defects lead to end stage renal failure and hypertension, and are associated with a high incidence of cardiovascular morbidity. Our lab focuses on understanding the molecular genetic basis of mammalian kidney development and on how disruption of specific pathways leads to abnormal development of this vital organ.

Mutations in the gene encoding for the zinc finger transcription factor SALL1 result in kidney, heart and other organ defects that define the autosomal dominant syndrome Townes-Brocks (TBS). Our lab has created a faithful mouse model of this syndrome and demonstrated that expression of a truncated mutant Sall1 protein is responsible for these developmental defects. Currently we are using genetic approaches in the mouse to define the role of Sall1 in kidney development and elucidate the pathogenesis of TBS. Genome wide screens using transcriptional profiling and chromatin immunoprecipitation (ChIP) are underway to define Sall1 target genes in the kidney.

Mutations in SALL4 cause the Okihiro and Holt-Oram syndromes, autosomal dominant disorders associated with multiple organ defects. Sall4 is also required for normal kidney and heart development. We are using Sall4 mouse mutants and reporter mice that express GFP in the developing kidney to uncover the function of Sall4 in proper outgrowth and branching of the ureter.

We discovered a novel 12 amino acid repression motif in Sall proteins (SRM) that recruits the nucleosome remodeling and deacetylase (NuRD) complex to regulate target gene expression. Sall1 target genes identified in our unbiased genome wide screens are being tested for NuRD dependent regulation. We are also using genetic approaches to define the role of specific NuRD componets, such as Mta2, in kidney development.

The kidney has the capacity to recover from acute ischemic and toxic insults by regenerating tubular epithelia. Reutilization of developmental pathways is thought to play a key role in this process. We are using ischemia reperfusion injury in adult mice to define the role of Sall1 and other developmental regulators in tissue regeneration in the kidney. Acute kidney injury is a common condition associated with poor outcomes in patients. Our long term goal is to understand how the repair process is regulated so that new therapeutic strategies can be developed.