Deconstructing and Reconstructing Human Disease Using Patient-Specific Stem Cells

Technical Focus:

Human Stem Cell Engineering

       There are many diseases for which no cures exist.  But even existing treatments need improvement.  For example, huge variability exists in patient responses to traditional pharmaceuticals, partly because patients metabolize drugs differently.  We need new cures, and they should ideally be personalized to maximize chances of success.

       Human induced pluripotent stem (iPS) cells are uniquely suited for these purposes.  These embryonic-like cells can be derived, now in a standardized manner, from virtually any patient sample - and be matured to make various patient-specific cells or tissues.  While human iPS cells capture genetic variation among patients and have potential to make any cell in the body, we still need better control both in time and space over these stem cells.  My interests lie in using human stem cells together with emerging engineering methods in material science and synthetic biology.  Successful experimentation with these techniques could yield new human disease models to dissect the basic biology of disease and smarter therapeutics and diagnostics for regenerative, translational, and personalized medicine.

      

Social Science/Policy Focus:

Constructing & Deconstructing Diseases in a Dish

       Scientists have long assumed that they study fundamentally natural biological entities.  Social scientific analysis however indicates that this assumption ignores built-in social commitments to ethical, moral, and political norms that influence the objects of scientific study. 

       Currently, new cellular models of human disease are emerging through the use of reprogramming technology.  Direct reprogramming of human somatic cells to embryonic-like induced pluripotent stem (iPS) cells uses readily accessible skin, fat, blood, and hair cells.  A primary use of such technology is to reprogram somatic cells from patients who are classified into a disease group, thus creating iPS cell lines popularly labeled as “diseases-in-a-dish.”  The disease-in-a-dish agenda thus frames disease as a phenomenon to be seen at the cellular level by laboratory scientists.

       Diseases have significant moral histories, both for an individual patient and for various collective social groups.  By drawing on analytical tools in both science and science studies, my work will examine the assumptions built into “diseases-in-a-dish.”  A small subset of neurodegenerative diseases will serve as initial case studies.  As these diseases in a dish are constructed through stem cell biology and engineering, laboratory work will be extended to examine the moral, economic, and political status of these objects.  Research results will be designed to invoke reflection among practicing scientists on the social commitments behind their choices when modeling a disease, as well as to inform regulations, institutional obligations, and state policy.

Advisors:

Rudolf Jaenisch (Whitehead Institute) 

Sheila Jasanoff (Science and Technology Studies Program - Harvard Kennedy School)