Harvard Fibrosis Network

In HSCI’s Harvard Fibrosis Network (HFN), our scientists look for commonalities across fibrotic diseases, sharing expertise in many different organs, biological processes and technical disciplines. Our unique approach brings academic, clinical, and pharmaceutical research practice to bear on fibrosis of the kidney, lung, heart, liver, skin and other organs.

In fibrosis, excess connective tissue forms in an organ or tissue. This process can help close wounds as part of tissue repair, but can become a problem when it causes tissue stiffness and irreversible cell loss, leading to distortion and dysfunction. Fibrosis plays a role in many major disease processes, including pulmonary fibrosis; cirrhosis; chronic kidney disease; cardiac, skin, and skeletal muscle fibrosis; and myelofibrosis.

HFN scientists are tackling the significant unmet need for therapeutics to treat fibrotic diseases. We leverage the similarities in fibrotic processes across different organ systems to accelerate discovery, and rapidly apply scientific knowledge and potential drug targets identified in one organ system to others. We bring together intellectual and physical resources to ensure that our scientists succeed:

• Leading scientific and clinical expertise from across Harvard schools and teaching hospitals
• HSCI’s demonstrated organizational success in facilitating collaborative initiatives
• Ready access to human tissue and a large number of animal models of disease
• Core facilities specializing in induced pluripotent stem cells, small molecule screening, and informatics
• Extensive bioengineering capabilities across the Harvard and Massachusetts Institute of Technology landscape
• Expertise in directed differentiation and organoid development, enabling the direct interrogation of human tissues
• A highly developed toxicology and biomarker knowledge base
• Comprehensive molecular imaging capabilities, including 1) the imaging and chemistry expertise needed to develop novel peptide- and antibody-based probes for visualizing biological processes involved in fibrosis, such as epithelial injury, vascular leak and collagen deposition, and cross-linking, and 2) PET and MRI technologies for visualizing drug targets in the target organ.

Our approach

Our integrated programs, often in collaboration with industry, are designed to identify genes and molecules that regulate various pathways and cell types in three different organ systems of fibrosis. The information we acquire from one experimental system is likely to impact the other systems. For example:

• G2/M cell cycle arrest and oxidized lipids are likely involved in critical ways in renal fibrosis, but are also likely linked to hepatic and pulmonary fibrosis. Additionally, diabetic nephropathy is another focus of our renal group. 
• Our labs’ work on novel targets in the activated hepatic stellate cell, such as specific long noncoding RNAs, is also likely to be applicable to pulmonary and renal fibrosis.

We take validated drug targets in one organ system of fibrosis and assess them in other model systems, so that knowledge obtained from one system is quickly applied to other organs that HFN studies. Since there is much overlap in fibrosis mechanisms among the kidney, lung, heart, liver, skin, bone marrow, and skeletal muscle, there are many synergies among the systems studied, and our overall endeavor is much greater than the sum of its individual components.

HFN meetings and HSCI’s cross-institutional infrastructure ensure that data generated in each individual organ system are rapidly applied to the others. Studies with our biotechnology and pharmaceutical collaborators are performed in ways that respect intellectual property.

A Sampling of Our Faculty

Heart fibrosis

Kidney fibrosis

Liver fibrosis

Lung fibrosis

Myelofibrosis

Skeletal muscle fibrosis

Skin fibrosis

Imaging

Tissue engineering and 3D printing/modeling