Sepehr Ehsani

Sepehr Ehsani
University College London | UCL · Department of Philosophy

PhD

About

45
Publications
4,978
Reads
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635
Citations
Additional affiliations
January 2015 - June 2016
Massachusetts Institute of Technology
Position
  • PostDoc Position
April 2013 - December 2014
Whitehead Institute for Biomedical Research
Position
  • PostDoc Position
Education
September 2008 - November 2012
University of Toronto
Field of study
  • Laboratory Medicine and Pathobiology
September 2004 - June 2008
University of Toronto
Field of study
  • Laboratory Medicine and Pathobiology

Publications

Publications (45)
Article
Full-text available
University Health Network (UHN) Pathology, in its capacity of providing neuro-oncologic care, now utilizes a laboratory information system (LIS), which was instituted in September 2001. For the 75 years preceding the LIS, more than 50 000 pathology reports exist in paper format. High-throughput automated scanning of the paper archives was employed...
Article
Full-text available
Seasonal variation in the occurrence of several classes of cancer has been observed in the past. However, evidence for such trends in adult central nervous system tumors is scant. We have analyzed the monthly occurrence rates of glioblastomas as well as carcinomas metastatic to the brain in 6,154 neurosurgical patients in Toronto selected from the...
Article
Full-text available
The evolutionary origin of prion genes, only known to exist in the vertebrate lineage, had remained elusive until recently. Following a lead from interactome investigations of the murine prion protein, our previous bioinformatic analyses revealed the evolutionary descent of prion genes from an ancestral ZIP metal ion transporter. However, the molec...
Preprint
Full-text available
The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we r...
Chapter
Full-text available
The mantra that “the best way to predict the future is to invent it” (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, qui...
Article
Full-text available
Following an analysis of the state of investigations and clinical outcomes in the Alzheimer's research field, I argue that the widely-accepted 'amyloid cascade' mechanistic explanation of Alzheimer's disease appears to be fundamentally incomplete. In this context, I propose that a framework termed 'principled mechanism' (PM) can help with remedying...
Article
Full-text available
The quest to determine the function of a protein can represent a profound challenge. Although this task is the mandate of countless research groups, a general framework for how it can be approached is conspicuously lacking. Moreover, even expectations for when the function of a protein can be considered to be 'known' are not well defined. In this r...
Chapter
The chapter “Analytic Philosophy for Biomedical Research: The Imperative of Applying Yesterday’s Timeless Messages to Today’s Impasses” was previously published non-open access. It has now been changed to open access under a CC BY 4.0 license and the copyright holder has been updated to “The Author(s).”
Article
Full-text available
The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we r...
Preprint
Full-text available
This paper is about interpreting the aim of Plato's Sophist in a linguistic framework and arguing that in its attempt at resolving the conundrum of what the true meaning and essence of the word "sophist" could be, it resembles a number of themes encountered in contemporary linguistics. I think it is important to put our findings from the Sophist in...
Preprint
Full-text available
Ever since the advent of molecular biology in the 1970s, mechanical models have become the dogma in the field, where a "true" understanding of any subject is equated to a mechanistic description. This has been to the detriment of the biomedical sciences, where, barring some exceptions, notable new feats of understanding have arguably not been achie...
Article
Full-text available
For the past several decades, biomedical research has principally been centered on molecular biology and genomic science. Although many molecular pathways and players in different disease and normal biological processes have been elucidated over this period, the much hoped-for “true” understanding of cellular and organismic functions has arguably n...
Article
Full-text available
Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson’s disease. Genome-wide screens in yeast identified 332 genes that impact α-syn...
Article
Full-text available
The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investiga...
Article
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Advances in biology have mostly relied on theories that were subsequently revised, expanded or eventually refuted using experimental and other means. Theoretical biology used to primarily provide a basis to rationally examine the frameworks within which biological experiments were carried out and to shed light on overlooked gaps in understanding. T...
Article
Full-text available
Human α-synuclein (SNCA) is a 140-amino-acid protein belonging to the three-member synuclein family. It has been extensively studied due to its misfolding/aggregation in and genetic linkage to neurodegenerative diseases, especially Parkinson's disease (PD). To better understand its biology, models of SNCA toxicity have been developed in budding yea...
Article
The disheartening results of recent clinical trials for neurodegenerative disease (ND) therapeutics underscore the need for a more comprehensive understanding of the underlying disease biology before effective therapies can be devised. One hallmark of many NDs is a disruption in protein homeostasis. Therefore, investigating the role of protein home...
Article
Full-text available
Knowledge of phenotypic changes the cellular prion protein (PrP(C)) contributes to may provide novel avenues for understanding its function. Here we consider data from functional knockout/down studies and protein-protein interaction analyses from the perspective of PrP's relationship to its ancestral ZIP metal ion transporting proteins. When approa...
Article
Full-text available
The advent of molecular biology has led to the identification of definitive causative factors for a number of diseases, most of which are monogenic. Causes for most common diseases across the population, however, seem elusive and cannot be pinpointed to a limited number of genes or genetic pathways. This realization has led to the idea of personali...
Article
Full-text available
The cellular prion protein (PrP(C)) was recently observed to co-purify with members of the LIV-1 subfamily of ZIP zinc transporters (LZTs), precipitating the surprising discovery that the prion gene family descended from an ancestral LZT gene. Here, we compared the subcellular distribution and biophysical characteristics of LZTs and their PrP-like...
Article
Full-text available
The central dogma of molecular biology, formulated more than five decades ago, compartmentalized information exchange in the cell into the DNA, RNA and protein domains. This formalization has served as an implicit thematic distinguisher for cell biological research ever since. However, a clear account of the distribution of research across this for...
Article
Full-text available
All cells must keep time to consistently perform vital biological functions. To that end, the coupling and interrelatedness of diverse subsecond events in the complex cellular environment, such as protein folding or translation rates, cannot simply result from the chance convergence of the inherent chemical properties of these phenomena, but may in...
Article
Full-text available
The evolutionary origins of vertebrate prion genes had remained elusive until recently when multiple lines of evidence converged to the proposition that members of the prion gene family represent an ancient branch of a larger family of ZIP metal ion transporters.11. Schmitt-Ulms G, Ehsani S, Watts JC, Westaway D, Wille H. Evolutionary descent of pr...
Article
Full-text available
Many open problems in biology, as in the physical sciences, display nonlinear and 'chaotic' dynamics, which, to the extent possible, cannot be reasonably understood. Moreover, mathematical models which aim to predict/estimate unknown aspects of a biological system cannot provide more information about the set of biologically meaningful (e.g., 'hidd...
Article
Full-text available
We recently documented the co-purification of members of the LIV-1 subfamily of ZIP (Zrt-, Irt-like Protein) zinc transporters (LZTs) with the cellular prion protein (PrP(C)) and, subsequently, established that the prion gene family descended from an ancestral LZT gene. Here, we begin to address whether the study of LZTs can shed light on the biolo...
Article
Full-text available
Prions are units of propagation of an altered state of a protein or proteins; prions can propagate from organism to organism, through cooption of other protein copies. Prions contain no necessary nucleic acids, and are important both as both pathogenic agents, and as a potential force in epigenetic phenomena. The original prions were derived from a...
Article
Full-text available
Prions are units of propagation of an altered state of a protein or proteins. Prions can propagate from cell to cell, and from organism to organism, through cooption of other protein copies. Prions contain no necessary nucleic acids, and are important both as both pathogenic agents, and as a potential force in epigenetic phenomena. The original pri...
Article
DJ-1 is a small but relatively abundant protein of unknown function that may undergo stress-dependent cellular translocation and has been implicated in both neurodegenerative diseases and cancer. As such, DJ-1 may be an excellent study object to elucidate the relative influence of the cellular context on its interactome and for exploring whether ac...
Article
Full-text available
The perception of time is an indispensable facet of human consciousness, and may in fact be dynamically present in primates and other species, albeit with different manifestations. Moreover, contrary to the physical measures of time, cognitive temporal perception may be subjectively affected by both internal and environmental cues. Here we review t...
Article
Prion diseases are fatal neurodegenerative diseases of humans and animals which, in addition to sporadic and familial modes of manifestation, can be acquired via an infectious route of propagation. In disease, the prion protein (PrP(C)) undergoes a structural transition to its disease-causing form (PrP(Sc)) with profoundly different physicochemical...
Article
Since its discovery over twenty years ago, both the phylogenetic origin and the cellular function of the prion protein (PrP) have remained enigmatic. The subsequent discovery of the PrP paralog Doppel (Dpl) has strengthened the argument that the copper-binding ability of PrP and Dpl may be part of their cellular function.Chemical crosslinking provi...
Article
Full-text available
The physiological environment which hosts the conformational conversion of the cellular prion protein (PrP(C)) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrP(C) interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the stu...
Article
Full-text available
In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of tw...
Article
Full-text available
In the more than 20 years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into the function of PrP may be obtained through a characterization of its molecular neighborhood. Quantitative interactome data revealed the spatial proximity of a subset of metal ion transp...
Article
We report the case of a 63-year-old man who developed an anaplastic oligoastrocytoma of the brain stem and midbrain 13 years after postoperative high-dose proton-photon radiation therapy for a recurrent low-grade chondrosarcoma of the skull base. To our knowledge, this is the first reported case of an anaplastic glioma after proton-photon irradiati...
Article
Full-text available
Editorial, University of Toronto Journal of Undergraduate Life Sciences (JULS); Spring 2008

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