Thomas Jefferson University

Jan B. Hoek

Joannes Hoek, PhD
Jan B. Hoek, PhD

Dr. Hoek received his early training with some of the leading investigators of the day in metabolism (HA Krebs, University of Oxford, UK), mitochondrial function (JM Tager and EC Slater, University of Amsterdam) and oxidative stress (L Ernster, University of Stockholm).  Through his career, he has retained an active interest in the impact of metabolic deregulation on disease. His work emphasizes the functional interconnections between cell signaling, metabolism and mitochondrial function. Currently, the focus of his lab is the elucidation of the molecular and cellular mechanisms underlying alcohol-induced cell and tissue dysfunction leading to alcohol-related diseases, specifically in the context of the regeneration response to liver damage by partial hepatectomy.   He applies a broad range of experimental and theoretical approaches to characterize changes in cell signaling, energy metabolism and stress signals associated with acute and chronic ethanol consumption in liver and other tissues and its effects on tissue repair responses to injury. Gene expression and microRNA profiling are used to characterize the transcriptional and microRNA regulatory network, and more specifically, to resolve the contributions of individual cells and cell types in the liver to the integrated proliferative response and to understand the nature of the defects in regeneration associated with chronic alcohol treatment.

At the cellular level, a computational modeling approach is being applied to identify feedback loops in cell signaling and metabolic networks that may affect the stability and response strength of cells.  Dr. Hoek’s interest in cell signaling and its deregulation in liver disease was the initial stimulus for an emphasis on a computational modeling analysis of cell signaling networks. This approach relies on a close collaboration with theoretical biologists and aims at integrating experimental and computational studies of the cell signaling responses in order to arrive at a more quantitative understanding of the network features of the signaling machinery. This work resulted in one of the first publications to provide a detailed computational model of the upstream elements of the EGF receptor signaling network (Kholodenko et al, J Biol Chem 1999), at a time when the potential of that approach was barely appreciated.

The further elaboration of the analysis of the EGFR signaling network in ongoing collaborations with the computational biology group of Dr. Boris Kholodenko (now at University College Dublin) has resulted in a large number of experimental and theoretical papers aimed at an integrative analysis of cell signaling. This marriage between experimental and computational analysis of the receptor tyrosine kinase signaling network also drives much of his current studies to elucidate the deregulation of signaling crosstalk in diseases such as cancer and the implications for chemotherapy. In addition, the lab is carrying out a computational modeling analysis of the formation of reactive oxygen species (ROS) in the mitochondrial respiratory chain, which has identified features of hysteresis and bi-stability in mitochondrial ROS formation that may have implications for the response to transient hypoxia.

Dr. Hoek has received national and international recognition for his work on alcohol metabolism and its impact on disease. He is the recipient of the 2009 Mark Keller Award and Honorary Lectureship from NIAAA/NIH and the 2010 Henry Begleiter Award for Excellence in Alcohol Research from the Research Society on Alcoholism (RSA). Dr. Hoek is Associate Editor for Reviews and Commentaries of Alcoholism, Clinical and Experimental Research (ACER), the flagship journal for alcohol research. Dr. Hoek receives research grant support from NIAAA/NIH and is the program director for an NIAAA-supported Institutional Training grant (T32) that is currently in its 26th year of support at Jefferson. In addition, he is the recipient of a Senior Scientist Research and Mentoring Award (K05) from NIAAA/NIH.