About

Kairos Shen is the Associate Professor of the Practice at MIT’s Center for Real Estate (CRE), where he teaches the Real Estate Development Studio. Between 2020 and 2024, he served as the Executive Director, overseeing the Master of Science in Real Estate Development degree program as well as the CRE’s industry relations and partnerships. He advocates for the CRE’s interdisciplinary curriculum of “City Making,” which draws on knowledge, research, and practice across design, city planning, public policy, finance, and real estate. The curriculum aims to prepare students to address complex urban challenges such as social equity, housing affordability, climate resiliency, and infrastructure rebuilding. Prior to his academic role at MIT, Mr. Shen was the Director of Planning at the Boston Redevelopment Authority, Boston’s Economic Development and Planning Agency, and served as Boston’s Chief City Planner for thirteen years. In this capacity, he worked closely with the Mayor of Boston to develop and implement city planning and economic development policies, contributing to major initiatives including the development guidelines for the Rose Kennedy Greenway, the South Boston Waterfront Innovation District, the refurbishment of Fenway Park, and the revitalization of Nubian Square. He is a graduate of Swarthmore College and holds a Master of Architecture from MIT.

Research topics

• Biology
• Virology
• Computer Science
• Cell biology
• Medicine
• Genetics
• Internal medicine
• Biochemistry
• Computational biology

Selected publications

• Rag GTPases Suppress Renal Cystic Disease by Inhibiting TFEB Independently of mTORC1

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-24

  preprintOpen access

  Abstract Aberrant mTORC1 activation in renal tubular epithelial cells (rTECs) is implicated as a critical driver of renal cystic diseases (RCDs), including autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis (TSC), yet its precise role remains unclear. Rag GTPases recruit mTORC1 to lysosomes, its intracellular activation site. Unexpectedly, we found that deleting RagA/B in rTECs, despite inhibiting mTORC1, triggers renal cystogenesis and kidney failure. We identify TFEB as the key driver of cystogenesis downstream of RagA/B loss and show that Rag GTPases, rather than mTORC1, are the primary suppressors of TFEB in vivo . We further highlight increased nuclear TFEB as a shared feature of several RCD models, whereas differences in mTORC1 activity may explain the variable efficacy of mTORC1 inhibitors. Finally, we provide evidence that nuclear TFEB, rather than mTORC1 activation, is a more consistent biomarker of cyst-lining epithelial cells in ADPKD. Overall, these findings challenge the prevailing view that mTORC1 hyperactivation is required for renal cystogenesis, which has important translational implications. Teaser A serendipitous finding uncovers the Rag GTPases as strong suppressors of renal cystogenesis with important disease implications.

  PublisherOA PDFDOI

• Abstract 2086 Local Changes, Global Impacts: Investigating How Local Manipulations Alter Global Conformations in the Rag GTPase Heterodimer Using smFRET

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  Balancing anabolic and catabolic processes is crucial for eukaryotic cells to coordinate nutrient and metabolite levels across organelles. Central to this regulation is the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which integrates nutrient signals from recycled organelles, lysosomes, and late endosomes. Activation of mTORC1 in nutrient-rich conditions requires its anchoring to lysosomes by the Rag GTPases. Here, I investigate how local manipulations, such as small-molecule binding and mutations, regulate the global conformation of the Rag GTPase heterodimer, and thus how amino acid signals are transmitted to mTORC1.

  PublisherOA PDFDOI

• Global conformation of the Rag GTPase heterodimer governs eukaryotic amino acid sensing

  Proceedings of the National Academy of Sciences · 2025-10-15

  articleOpen accessSenior authorCorresponding

  The Rag GTPase heterodimer is a central mediator of amino acid sensing in eukaryotic cells. When amino acids are abundant, it binds to the mechanistic target of rapamycin complex 1 to activate cellular programs for growth and proliferation. In its functional cycle, besides local conformational changes near the nucleotides that are commonly observed in monomeric signaling GTPases, the relative positioning of the two Rag subunits, i.e., the global conformation, is unique due to the heterodimeric architecture. Although various global conformations have been captured in static structural models, dynamic transitions between these conformations and their biological relevance remain unclear. Here, we visualize the global conformation of the Rag GTPase heterodimer using single-molecule Förster resonance energy transfer. By tracking the movement of individual protein molecules, we found that the two subunits explore a wide conformational space, which is strictly dictated by the bound nucleotides, regulators, and mutations. Additionally, we demonstrate that proper modulation of the global conformation is crucial for correctly interpreting amino acid signals. Our results defined a checkpoint of amino acid sensing in eukaryotic cells.

  PublisherOA PDFDOI

• Structures and Functions of the Human GATOR1 Complex

  Sub-cellular biochemistry/Subcellular biochemistry · 2024-01-01 · 2 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Supplementary Table 2 from A Diverse Array of Cancer-Associated <i>MTOR</i> Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

  2023-04-03

  supplementary-materialsOpen access

  <p>XLSX file 31K, All MTOR mutations from a literature search and the cBIO, COSMIC, and ICGC databases are listed</p>

  PublisherDOI

• Supplementary Figure and Table Legends from A Diverse Array of Cancer-Associated <i>MTOR</i> Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

  2023-04-03

  preprintOpen access

  <p>PDF file 82K, Supplementary Figure and Table Legends</p>

  PublisherDOI

• Detergent modulates the conformational equilibrium of SARS-CoV-2 Spike during cryo-EM structural determination

  Nature Communications · 2023-05-03 · 17 citations

  articleOpen accessSenior author

  The Spike glycoprotein of SARS-CoV-2 mediates viral entry into the host cell via the interaction between its receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2). Spike RBD has been reported to adopt two primary conformations, a closed conformation in which the binding site is shielded and unable to interact with ACE2, and an open conformation that is capable of binding ACE2. Many structural studies have probed the conformational space of the homotrimeric Spike from SARS-CoV-2. However, how sample buffer conditions used during structural determination influence the Spike conformation is currently unclear. Here, we systematically explored the impact of commonly used detergents on the conformational space of Spike. We show that in the presence of detergent, the Spike glycoprotein predominantly occupies a closed conformational state during cryo-EM structural determination. However, in the absence of detergent, such conformational compaction was neither observed by cryo-EM, nor by single-molecule FRET designed to visualize the movement of RBD in solution in real-time. Our results highlight the highly sensitive nature of the Spike conformational space to buffer composition during cryo-EM structural determination, and emphasize the importance of orthogonal biophysical approaches to validate the structural models obtained.

  PublisherOA PDFDOI

• Supplementary Table 4 from A Diverse Array of Cancer-Associated <i>MTOR</i> Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

  2023-04-03

  supplementary-materialsOpen access

  <p>XLSX file 12K, All activating MTOR mutations from this study are listed</p>

  PublisherDOI

• Driver Fatigue Detection Using OpenCV and Dlib Library

  2023-12-04 · 6 citations

  article1st authorCorresponding

  Driver fatigue and distraction are major contributors to fatal road accidents worldwide. To enhance vehicle safety, this article proposes a fatigue detection system using EAR and MAR algorithms to identify signs of fatigue, such as eye closure and yawning. When prolonged eye closure or yawning is detected, the system issues an alert to the driver. It leverages OpenCV and Dlib libraries for implementation. Additionally, the system detects driver distraction by monitoring head swivels, counting left and right movements. It's worth noting that Dlib may yield facial landmark deviations for non-frontal faces. To mitigate this, the study selected 69 videos from the YawDD database, focusing on near-frontal face views, achieving a 91.3% accuracy rate.

  PublisherDOI

• Supplementary Figure 6 from A Diverse Array of Cancer-Associated <i>MTOR</i> Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

  2023-04-03

  preprintOpen access

  <p>PDF file 154K, Recurrent mTOR mutations mapped onto the crystal structure of mTOR</p>

  PublisherDOI

Recent grants

• A Molecular Study of Rag GTPase-Dependent Amino Acid Sensing

  NIH · $204k · 2020–2022

• Spatial and temporal regulation of nutrient sensing

  NIH · $1.8M · 2022–2027

Frequent coauthors

• David M. Sabatini

  Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

  318 shared

• Lynne Chantranupong

  Howard Hughes Medical Institute

  94 shared

• Pascal Houillier

  Université Paris Cité

  92 shared

• Rachel L. Wolfson

  Harvard University

  63 shared

• Gregory A. Wyant

  Harvard University

  60 shared

• Andrew H. Beck

  AstraZeneca (United Kingdom)

  57 shared

• Sumi Sinha

  57 shared

• Valentina Nardi

  57 shared

Education

• PhD, Chemistry and Chemical Engineering

  California Institute of Technology

  2013

• BS, School of Chemistry and Materials Science

  University of Science and Technology of China

  2007