Post-doc position on Shh dynamics in limb development at NIH

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Limb development as a model for regulation and evolution of vertebrate form:  Fellowship position to investigate dynamics of Shh regulation and function.

Mackem lab is recruiting for NIH-funded post-doc position in developmental morphogenesis to study the roles of Shh in vertebrate limb patterning (different digit types, numbers, adaptations) using molecular-genetic and genomic approaches.  Our long-term goal is understanding how regulatory networks instruct the formation of complex structures with distinct shapes, such as the varying bony segments and joint numbers in different digits, arising from the same tissues and not based in cell fate changes per se.  

Current work focuses on genome-wide approaches to identify key Shh relay signals and their relation to late signaling centers, comparative evolutionary analyses to reveal regulatory mechanisms underlying morphology-based adaptations and combined genetic/genomic strategies to explore the dynamic, robust nature of Shh-producing cells. We recently showed that Shh acts as a trigger, not morphogen, to initiate digit patterning, but the critical targets remain unknown.  We have discovered that the Shh-producing ZPA domain in the limb is not a static population but arises from progenitors at the limb border that contribute to ongoing ZPA renewal and plan to characterize progenitor pool regulation.  We have also found that the widespread phenomenon of autocrine non-responsiveness in Shh-producing cells is an intrinsic feature of these cells, not due to negative-feedback, and are examining its mechanistic basis.       

Applicants should have a strong background in developmental and/or evo-devo biology. Prior experience with cutting-edge genomic approaches is desirable.  For more information, please contact Susan Mackem (mackems@mail.nih.gov) directly.

Recent lab publications:

Huang et al. (2026) Nature Communications.   A pivotal Wnt antagonist role promoting digit joint specification by constraining Wnt activity.  In press May 2026.  doi.org/10.1038/s41467-026-73549-4

Patel and Mackem (2025) PNAS.  Dual Bmp-negative feedback loops modulate function of both AER and ZPA to buffer and constrain postaxial digit number.  122: e2427249122. doi.org/10.1073/pnas.2427249122

Zhu et al. (2022) Dev Cell.  Sonic hedgehog is not a limb morphogen but acts as a trigger to specify all digits in mice. 57: 2048-62.

Trofka et al. (2021) Current Biology. Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates. 31: 4923-34.

Reviews/perspectives:

Huang et al. (2022) Dev. Dynamics. Rethinking positional information and digit identity: The role of late interdigit signaling.   251:1414–1422.

Zhu et al. (2017) Dev. Biology.  John Saunders’ ZPA, Sonic hedgehog and digit identity – How does it really all work?    429:391-400.

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