Education & Training
- MD, University of Western Ontario, 2001
- MSc, Developmental Biology, University of Toronto, 1997
- BSc, Genetics, University of Western Ontario, 1995
Research Interest Summary
Chronic kidney disease (CKD) is a growing public health burden that results in significant morbidity and increased risk of mortality for individual patients. In the United States alone, the cost of care for CKD, kidney transplant and dialysis is over 40 billion dollars annually. At present, there are limited therapies available to ameliorate the progressive loss of renal function in CKD, and this ultimately leads to dialysis or transplant for these patients. Thus, there is an urgent need to develop novel tools and resources that may lead to innovative strategies to enhance renal repair and promote the generation of new nephrons in future.
In the pediatric population, renal dysplasia/hypoplasia is a leading cause of renal failure in children, and the risk of chronic kidney disease is linked to decreased renal reserve as a result of the formation of fewer and/or abnormal nephrons during kidney development. Furthermore, decreased congenital nephron endowment is associated with adult onset hypertension, a common health problem that leads to decreased life expectancy. Understanding the molecular mechanisms that control nephron number and formation is critical to making an impact on these diseases.
My laboratory is focused on understanding how microRNAs (miRNAs) regulate kidney development and disease. MiRNAs are small, non-coding RNA molecules that function largely as negative regulators of gene expression, and while they have been implicated in stem cell biology and the development of other organs, little is known about their role in the kidney [3, 4]. Nephron progenitors represent a population of self-renewing, multipotent progenitor cells that give rise to all the epithelial components of the nephron, the functional unit of the kidney. To make an impact on patients with CKD, we are studying the role of miRNAs in nephron progenitors, as a means of both understanding how nephron number and formation is determined during kidney development, and how one might propagate and manipulate nephron progenitors for novel renal regenerative therapies.
Ho J, Ng KH, Rosen S, Dostal A, Gregory RI and Kreidberg JA. Podocyte-specific loss of functional miRNAs leads to rapid glomerular and tubular damage. J Am Soc Neph 2008; 19(11): 2069-2075. PMID: 18832437.
Ho J, Pandey P, Schatton T, Sims-Lucas S, Khalid M, Frank MH, Hartwig S and Kreidberg JA+. The pro-apoptotic protein Bim is a microRNA target in kidney progenitor cells. J Am Soc Neph 2011; 22(6): 1053-1063. PMID: 21546576.
Chu JYS, Sims-Lucas S, Bushnell DS, Bodnar AJ, Kreidberg J and Ho J. Dicer function is required in the metanephric mesenchyme in early kidney development. Am J Physiol Renal Physiol 2014; 306(7): F764-72. PMID: 24500693.
Marrone AK, Stolz DB, Bastacky SI, Kostka D, Bodnar AJ and Ho J. miR-17~92 is required for nephrogenesis and renal function. J Am Soc Neph 2014; 25(7): 1440-1452. PMID: 24511118.
Cerqueira DM, Bodnar AJ, Phua YL, Freer R, Hemker SL, Walensky LD, Hukriede NA and Ho J. Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development. FASEB J, 2017 Aug; 31(8): 3540-3554. PMID: 28446592.
Phua YL, Chen KH, Hemker SL, Marrone AK, Bodnar AJ, Liu X, Clugston A, Kostka D, Butterworth MB and Ho J. Loss of miR-17~92 results in dysregulation of Cftr in nephron progenitors. Am J Physiol Renal Physiol, 2019 May 1;316(5):F993-F1005. PMID: 30838872.
Cerqueira DM, Hemker SL, Bodnar AJ, Ortiz DM, Oladipupo FO, Mukherjee E, Gong Z, Appolonia C, Muzumdar RH, Sims-Lucas S and Ho J. In utero exposure to maternal diabetes impairs nephron progenitor differentiation. Am J Physiol Renal Physiol, 2019 Nov 1;317(5):F1318-F1330. PMID: 31509011. *APS Select article, recognizing distinction in scholarship.
Hemker SL, Cerqueira DM, Bodnar AJ, Cargill KR, Clugston A, Anslow MJ, Sims-Lucas S, Kostka D and Ho J. Deletion of hypoxia-responsive microRNA-210 results in a sex-specific decrease in nephron number. FASEB J. 2020 Mar 5; doi: 10.1096/fj.201902767R. [Epub ahead of print] PMID: 32141129.