Hsu Laboratory

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Research

Mammalian organs are complex structures composed of precise integration of cells from diverse lineages. Successful regeneration of a fully functional organ relies on timely and coordinated behaviors among different cell types and lineages.

We use a wide variety of approaches and techniques, including molecular, cellular, genetic and genomic tools, to investigate how stem cell behaviors are regulated by their downstream progeny, their niches, and at the systemic level. We aim to understand how these regulations occur in a precise manner to meet various physiological demands, and how deregulated stem cell behaviors lead to diseases. Skin is our primary model system, but we are also exploring other epithelial tissues to determine the extent to which these mechanisms are shared or separate.

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Cell-Cell Interaction during Development, Regeneration, and Disease

The skin protects us from infection and dehydration. It also enables thermoregulation and sensory perception. These multifaceted functions are accomplished by a rich diversity of cell types, necessitating multiple reservoirs of stem cells. Each lineage within the skin is spatially defined. The epidermis and its appendage the hair follicle are among the few organs in mammals that undergo natural regeneration throughout life. The epidermis and hair follicles are maintained by separated pools of stem cells. The epidermis regenerates continually while hair follicles undergo cycles of growth (anagen), degeneration (catagen), and rest (telogen). The rich diversity of cell types and the highly regenerative feature together makes skin an ideal paradigm to study how different cells influence one another during development and regeneration. Our research interests are focused on the following area:

Feedback Regulation from Stem Cell Progeny:

We are among the pioneers to identify stem cell progeny as important regulators of their stem cell parents. Currently, we are elucidating specific signalling molecules governing these feedback regulations.

Niche – Stem Cell Crosstalk:

We are exploring novel niche components that regulate different populations of skin stem cells. Our ultimate goal is to apply the knowledge we learned form our studies to reconstitute a fully functional skin for tissue replacement, which remains as a great challenge for treating burn patients.

Alternation of Niches in Diseases:

Diseases such as chronic wounds and skin cancer often involve alteration of niches. We aim to understand how changes in niche signalling contribute to the progression of these diseases.

Teaching

SCRB 145

From Cells to Tissues, in Sickness and in Health

Every cell is a part of a larger “community”, working together to enable tissue function. This course will explore the principles of building complex tissues from cells. How do cells know what tissues to make and when to make them? How do cells communicate with one another? What diseases can arise when these principles go awry? How can we build tissues in the lab? In addition to lectures, students will engage deeply in primary literature. 

Syllabus

DRB 331

Critical Analysis and Experimental Approaches in Developmental Biology

This course will provide a survey of major topics and contemporary research in developmental and regenerative biology. Students will rotate in the laboratories of DRB faculty across the Harvard campuses and affiliated hospitals. Students engage with faculty and gain hands on experience in a variety of model systems, techniques and research areas. Each day of the course will consist of a lecture followed by hands-on laboratory activities and interactive discussions. Students will be required to complete the lab experience and the following assignments: lead two chalk-talk format paper presentations, and write one 5-6 page research proposal.

Announcements

We are seeking motivated and creative Postdocs and Graduate Students. If you are fascinated about the highly regenerative nature of the mammalian skin, intrigued by the complexity of cell-cell communication, ever wondered about how sensitive our skin and hairs are to various changes, and if you like to build a dynamic, passionate, and interactive lab environment together with us, we would love to have you here!

Please contact Ya-Chieh directly if you are interested in joining us. For postdoc applicants, please include the following materials in your email:

  • Cover letter (including a short summary of your current research and future interests. In addition, please let us know if you are particularly interested in a specific area of our research, or how our expertise might help you develop independent projects to further your research goals)
  • CV
  • Contact information of three references

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