About

Daniel S. Kessler, Ph.D., is an Associate Professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania. He serves as the Chair of the Institutional Biosafety Committee, Co-Director of PennPREP, and Associate Dean of Graduate Education, overseeing the Biomedical Graduate Studies Department. His research focuses on the establishment and organization of the primary germ layers, formation and function of the Spemann organizer in axial development, and the signaling and transcriptional networks involved in vertebrate gastrula development. Using biochemical, molecular, genomic, and embryological approaches with model organisms such as Xenopus and zebrafish, his work aims to elucidate the transcriptional regulatory pathways that pattern the embryo and how inductive signals generate distinct cellular responses during development. His studies have identified key transcriptional cascades and regulatory genes, including Siamois, Twin, Goosecoid, Nodal, VegT, FoxD3, Sox17, and others, which are essential for germ layer formation and organizer function. Dr. Kessler's contributions advance understanding of vertebrate embryogenesis, particularly in the context of body plan establishment and signaling center formation.

Research topics

• Biology
• Cell biology
• Molecular biology
• Genetics
• Anatomy

Selected publications

• Signal Transduction and Transcriptional Regulation in the Response to Type I Interferon

  Digital Commons - RU (Rockefeller University) · 2025-09-08

  articleOpen access1st authorCorresponding

  The interaction of type I interferon (IFN) with a specific cell surface receptor elicits a number of physiological changes, including the attainment of a state in which viral replication and cellular proliferation is inhibited. The response to IFN is mediated by a group of IPN-induced proteins which are regulated at the transcriptional level. Therefore, a central event in the cellular response to IFN is the coordinate transcriptional induction of a specific set of interferon stimulated genes (ISGs). In this thesis, I have addressed the cellular strategies employed to transmit specific cell surface signals across compartmental boundaries, ultimately resulting in specific transcriptional modulation in the nucleus. The analysis of the 5' regulatory sequences of two ISGs has identified a conserved interferon stimulated response element (ISRE) present in all ISGs, which is necessary and sufficient for transcriptional responsiveness to IFN. Three nuclear DNA-binding factors were identified that specifically bind the ISRE, one which was constitutive and two whose presence was dependent of IFN treatment. The analysis of the kinetics, protein synthesis-dependence, and precise sequence requirements for ISRE binding of these interferon stimulated gene factors (lSGFs) implicated a single IFN-inducible factor, ISGF3, as the positive regulator of ISGs. ISGF3 was induced rapidly in the absence of ongoing protein synthesis, characteristics identical to transcriptional activation of ISGs. The study of IFN-resistant variant cell lines which do not respond to IFN physiologically, but do express normal IFN receptors, supported the role of ISGF3 as the ISG activator. In these resistant cell lines the lack of ISG induction correlated with a defect in ISGF3 activation. Furthermore, it was found that ISGF3 activation occurred in the cytoplasm of stimulated cells through a series of events involving post-translational activation of a latent cytoplasmic protein, and subsequent association with a second cytoplasmic protein forming a heteromeric complex which accumulated in the nucleus. Additional characterization of the ISGF3 complex revealed a heterotetromeric complex (48, 84, 91, and 113 kD subunits). The activation and formation of ISGF3 required IFN-dependent post-translational activation of at least one of the high molecular weight subunits (84, 91, or 113 kD), leading to facilitated nuclear translocation of this group of three proteins. Upon nuclear accumulation these proteins associated with the 48 kD ISRE-binding subunit resulting in an enhancement of DNA binding affinity and formation of the stable, transcriptionally active ISGF3- ISRE complex. In the type I IFN system, specific transcriptional regulation in response to a cell surface ligand is mediated by activation of a latent cytoplasmic transcription factor which is a highly specific intracellular messenger.

  PublisherOA PDFDOI

• The evolutionary loss of the Eh1 motif in FoxE1 in the lineage of placental mammals

  PLoS ONE · 2023-12-27

  articleOpen accessCorresponding

  Forkhead box E1 (FoxE1) protein is a transcriptional regulator known to play a major role in the development of the thyroid gland. By performing sequence alignments, we detected a deletion in FoxE1, which occurred in the evolution of mammals, near the point of divergence of placental mammals. This deletion led to the loss of the majority of the Eh1 motif, which was important for interactions with transcriptional corepressors. To investigate a potential mechanism for this deletion, we analyzed replication through the deletion area in mammalian cells with two-dimensional gel electrophoresis, and in vitro, using a primer extension reaction. We demonstrated that the area of the deletion presented an obstacle for replication in both assays. The exact position of polymerization arrest in primer extension indicated that it was most likely caused by a quadruplex DNA structure. The quadruplex structure hypothesis is also consistent with the exact borders of the deletion. The exact roles of these evolutionary changes in FoxE1 family proteins are still to be determined.

  PublisherOA PDFDOI

• FoxH1 mediates a Grg4 and Smad2 dependent transcriptional switch in Nodal signaling during Xenopus mesoderm development

  Developmental Biology · 2016-04-13 · 13 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Digitale Transformation

  2015-01-01 · 10 citations

  book-chapter
  PublisherDOI

• LRRK2 Transport Is Regulated by Its Novel Interacting Partner Rab32

  PLoS ONE · 2014-10-31 · 97 citations

  articleOpen access

  Leucine-rich repeat kinase 2 (LRRK2) is a multi-domain 280 kDa protein that is linked to Parkinson's disease (PD). Mutations especially in the GTPase and kinase domains of LRRK2 are the most common causes of heritable PD and are also found in sporadic forms of PD. Although the cellular function of LRRK2 is largely unknown there is increasing evidence that these mutations cause cell death due to autophagic dysfunction and mitochondrial damage. Here, we demonstrate a novel mechanism of LRRK2 binding and transport, which involves the small GTPases Rab32 and Rab38. Rab32 and its closest homologue Rab38 are known to organize the trans-Golgi network and transport of key enzymes in melanogenesis, whereas their function in non-melanogenic cells is still not well understood. Cellular processes such as autophagy, mitochondrial dynamics, phagocytosis or inflammatory processes in the brain have previously been linked to Rab32. Here, we demonstrate that Rab32 and Rab38, but no other GTPase tested, directly interact with LRRK2. GFP-Trap analyses confirmed the interaction of Rab32 with the endogenous LRRK2. In yeast two-hybrid experiments we identified a predicted coiled-coil motif containing region within the aminoterminus of LRRK2 as the possible interacting domain. Fluorescence microscopy demonstrated a co-localization of Rab32 and LRRK2 at recycling endosomes and transport vesicles, while overexpression of a constitutively active mutant of Rab32 led to an increased co-localization with Rab7/9 positive perinuclear late endosomes/MVBs. Subcellular fractionation experiments supported the novel role of Rab32 in LRRK2 late endosomal transport and sorting in the cell. Thus, Rab32 may regulate the physiological functions of LRRK2.

  PublisherOA PDFDOI

• 468 Concerted Action of Rab11 and Rab25 in Vesicle Trafficking During Cell Migration

  European Journal of Cancer · 2012-07-01

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• The Action of Small GTPases Rab11 and Rab25 in Vesicle Trafficking During Cell Migration

  Cellular Physiology and Biochemistry · 2012-01-01 · 44 citations

  articleOpen access1st authorCorresponding

  BACKGROUND: The closely related GTPases Rab11 and Rab25 promote cell migration by regulating vesicular transport and recycling of surface receptors. Rab25 carries a constitutively activating mutation in its GTPase domain. Increased expression of Rab25 has been associated with the aggressiveness of migrating tumor cells. Here, we aimed to elucidate potential differences in the role of those two GTPases in vesicle trafficking during cell migration. METHODS: We expressed Rab11 and Rab25 wildtype and mutant constructs in HeLa and MDA-MB231 cells and measured their effect on cell morphology, vesicle dynamics and migration behaviour. In prostate cancer samples we analyzed the expression of both GTPases. RESULTS: Cells grown on fibronectin displayed a more stretched morphology when Rab11 was inactivated, whereas inactivation of Rab25 led to reduced stretching. Overexpression of both Rab11 and Rab25 accelerated cell migration. Analysis of vesicular movement revealed higher transport efficiency in the inner cell compartment for Rab11 positive vesicles and in proximity to the membrane for Rab25 positive vesicles. Interestingly, we found Rab25 to be highly expressed in prostate cancer tissue. CONCLUSION: Taken together, our data suggest that Rab11 is mainly responsible for basal long-distance transport from the rear end to the front of the migrating cell, whereas Rab25 acts predominantly in the small-scale fast recycling within the tips of the cell. Our results further support the idea of Rab25 as a promoter of tumor development.

  PublisherOA PDFDOI

• Transcriptional integration of Wnt and Nodal pathways in establishment of the Spemann organizer

  Developmental Biology · 2012-05-22 · 27 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• A phylogenetic tree for proteins of the FoxE subclass and the FoxC and FoxD outgroups

  Figshare · 2011-01-01

  articleSenior author

  <b>Copyright information:</b>Taken from "Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators"http://www.biomedcentral.com/1471-2164/8/201BMC Genomics 2007;8():201-201.Published online 28 Jun 2007PMCID:PMC1939712. A neighbor-joining method was used to construct the tree topology and bootstrapping values are shown at each branch point (percentage of 1000 bootstrap samples) using the MEGA 3.1 software. Gaps were deleted in pairwise comparisons. The distance scale below the tree represents the number of substitutions per site. The C and D families are collapsed for better illustration. Protein sequences that lack a recognizable eh1-like motif are represented by blue triangles. Proteins and subclasses that contain an eh1-like motif are represented by red circles.

  DOI

• Siamois and Twin are redundant and essential in formation of the Spemann organizer

  Developmental Biology · 2011-02-04 · 29 citations

  articleSenior authorCorresponding
  PublisherDOI

Recent grants

• Negative Regulation of TGFß Signaling by a Fast1-Groucho Corepressor Complex

  NSF · $280k · 2007–2011

• NIH Grant R01HD035159

  NIH · $2.5M · 2007

• NIH Grant R01NS041005

  NIH · $1.4M · 2005

• NIH Grant R01GM064768

  NIH · $2.6M · 2012

Frequent coauthors

• Douglas A. Melton

  University of Missouri

  17 shared

• David E. Levy

  New York University

  15 shared

• Christine D. Reid

  12 shared

• Sergey Yaklichkin

  Memorial Sloan Kettering Cancer Center

  9 shared

• Qun Lu

  Air Force Medical University

  9 shared

• Shouwen Wang

  China Three Gorges University

  7 shared

• Aaron B. Steiner

  Pace University

  7 shared

• James Darnell

  Rockefeller University

  7 shared

Labs

• Daniel S. Kessler LabPI

Education

• Postdoctoral Fellow, Developmental Biology, Molecular and Cellular Biology

  Harvard University

  1995

• Postdoctoral Fellow, Molecular Biology, Pathology

  New York University Grossman School of Medicine

  1991

• PhD, Molecular Biology, Laboratory of Molecular Cell Biology

  Rockefeller University

  1990

• BS, Biology (Genetics and Development)

  Cornell University

  1986