Ben Fogelgren grew up in central Virginia and attended college at the University of Pennsylvania in Philadelphia, where he received his Bachelor of Science in Engineering (BSE) in Bioengineering in 1997. While an undergraduate student, Ben worked in the laboratory of Dr. Jaclyn Biegel in the Genetics Division at the Children’s Hospital of Philadelphia. This lab was focused on identifying genetic causes of pediatric brain tumors, and it was this experience that motivated him to pursue a career in biomedical research. Ben received his Ph.D. in 2005 in Cell and Molecular Biology at the John A. Burns School of Medicine at the University of Hawaii. Ben’s graduate studies in the lab of Dr. Katalin Csiszar focused on identifying regulatory mechanisms of the extracellular enzyme lysyl oxidase, and how these mechanisms can influence cancer metastasis and tissue fibrosis.
For the next few years, Ben did postdoctoral training with Dr. Scott Lozanoff in the Department of Anatomy, Biochemistry, and Physiology (University of Hawaii), studying the genetics of kidney development and renal physiology using cell culture and animals models. In 2008, Ben went back to Philadelphia for postdoctoral training with Dr. Joshua Lipschutz in the Renal-Electrolyte and Hypertension Division of the University of Pennsylvania School of Medicine. During this time, Ben’s research focused on epithelial primary cilia, polarized intracellular trafficking, and 3D epithelial morphogenesis, all in the context of complex renal diseases like polycystic kidney disease. In 2011, Ben was recruited back to the Department of Anatomy, Biochemistry, and Physiology at the John A. Burns School of Medicine (University of Hawaii) as a tenure track Assistant Professor. Ben joined the Institute for Biogenesis Research in 2013, and was promoted to Associate Professor (with tenure) in 2017.
Our research is focused on the molecular and genetic causes of abnormal kidney development, as well as the novel causes and treatments of adult renal diseases such as polycystic kidney disease and acute renal injury. The same molecular signals and cellular morphogenesis patterns that we study in the kidney can also give us novel insights into development of other tissues, as well as teach us how these processes can be disrupted in a large variety of diseases.
Cysts and tubules are primary building blocks of the kidney, and defects in cystogenesis or tubulogenesis during kidney development can result in a spectrum of pediatric and adult renal diseases. Relevant to our research, during kidney development, disruption in the formation of de novo epithelial cysts from pools of mesenchymal stem cells lead to various forms of congenital abnormalities such as kidney hypoplasia, dysplasia, or agenesis. On the other hand, following nephrogenesis, when the inhibitory signals that halt excessive cyst formation are disturbed, forms of renal disease such as polycystic kidney disease (PKD) can occur. Autosomal dominant PKD (ADPKD), which affects approximately 500,000 Americans and currently has no approved treatment, is the most common potentially lethal genetic disease. Every variation of human PKD has been attributed to mutations in genes important to the assembly or function of the primary cilium, a thin rod-like organelle on renal tubular epithelial cells which projects into the tubular lumen (See Figure 1).
Primary cilia have been found on the surface of most growth-arrested or differentiated mammalians cells, including a large variety of epithelial cells, endothelial cells, connective-tissue and muscle cells, as well as neurons and even embryonic stem cells. Although the presence of primary cilia has been noted for over a hundred years, its biological function was a mystery. Due to an exploding volume of research in just the last decade, it is now believed the primary cilium acts as a “sensory antenna” to relay signals to the cell based on the extracellular environment. These can include sensory clues such as mechanical stimulation (bending or rotation), chemosensation (detection of growth factors, morphogens, etc.), osmolarity, light, temperature, and even gravitational pull. It is thought that primary cilia along the renal tubules are responsible for detecting fluid composition and flow dynamics, and when defective, the cells misinterpret this as a signal to dedifferentiate and proliferate, resulting in the formation of large pathogenic renal cysts. However, defects in primary cilia can affect other tissues as well, and have resulted in a new classification of human disorders termed “ciliopathies”.
Currently, we have research projects focused both on the molecular mechanisms of de novo cyst formation, and on primary cilia assembly and signaling. We have found both of these cellular activities depend on the exocyst complex, a highly conserved eight-protein complex (see Figure 2), which is involved in targeted secretory vesicle transport. We are working hard to discover how cells regulate the exocyst subunits in order to direct polarized trafficking to specific locales such as primary cilia and the lumens of growing epithelial cysts. These discoveries may lay the groundwork for novel therapies for adult and pediatric renal diseases, and expand our knowledge of some of the basic cellular and molecular mechanisms by which the human body controls its development.