Location

Rochester, Minnesota

Contact

Sussman.Carli@mayo.edu

Summary

The kidney is comprised of several cell types, which are organized into a complex network of tissues for processing the blood and regulating the final composition of urine.

Many processes involved in kidney development are also required for proper kidney maintenance and function. We focus on pathogenic alterations in kidney development and maintenance leading to cyst formation and polycystic kidney disease (PKD).

PKD is primarily characterized by progressive renal cyst formation ultimately causing renal failure. It occurs in two major forms, autosomal dominant (ADPKD) and autosomal recessive (ARPKD). ADPKD is the most common genetic cause of renal failure. It often presents in the prime of life (third to fourth decades) and accounts for approximately 10% of patients with end stage renal disease and almost 10% of patients receiving dialysis. ARPKD is less common but more severe, causing approximately 30% mortality within the first year of life.

Mutations in Polycystin-1, Polycystin-2, and Fibrocystin/Polyductin proteins account for most, but not all, cases of PKD. Additionally, variability in the onset and severity of PKD indicate the importance of additional modifier proteins in the etiology of PKD. This is especially true for the more prevalent, autosomal dominant form. Identification of modifier and novel causal proteins is critical for their diagnostic and prognostic value, and for development of new therapeutics.

We are using zebrafish to characterize putative novel modifier and causal proteins in PKD. The zebrafish model system has several advantages for these studies. Zebrafish have external fertilization, thus kidney development is readily visible throughout embryogenesis. The relevance of several zebrafish models of PKD have been demonstrated. That is, similar morphological and physiological changes occur in zebrafish in response to alteration of proteins involved in PKD in humans.

Most notably, zebrafish develop dilation of renal tubules, renal cysts, and impaired fluid balance and renal function. These validated zebrafish models of PKD are useful for assessing contributions of additional candidate proteins to PKD. The genetic tractability of zebrafish facilitates in vivo studies targeting specific proteins, and there are several lines of renal fluorescent reporter fish to facilitate detection of renal effects.

Recent Publications

See my publications

Professional Details

Primary Appointment

  1. Physiology and Biomedical Engineering

Academic Rank

  1. Assistant Professor of Physiology

Education

  1. Post Doctoral Fellowship - Regulation of Oligodendrocyte Lineage Development Department of Neuroscience, Case Western Reserve University
  2. PhD - Physiology University of Connecticut
  3. Post Doctoral Fellowship - Molecular Mechanisms of Bicarbonate Transport Department of Cellular and Molecular Physiology, Yale University
  4. MS - Physiology University of Connecticut
  5. BA - Biology Connecticut College
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BIO-00095375

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