BE Seminars & Events

Current Seminar Series: 2016-2017

Bioengineering Seminars are held on Thursdays at 10:30AM in 337 Towne Building unless otherwise noted below. For all Penn Engineering events, visit the Penn Calendar.

  September 8
Glen Niebur
TBA
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TBA

  October 6
No Seminar
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TBA

 

Monday, October 17
Joint Seminar
Orion Weiner
TBA

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October 20
Jennifer Cochran
Engineering proteins for visualizing and treating cancer

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We engineer proteins as therapeutics and diagnostic agents for biomedical applications including cancer and regenerative medicine. I will discuss the discovery and development of novel therapeutic approaches to targeted cancer treatment, spanning a broad range of efforts in the areas of protein engineering, biochemical and biophysical analyses, and preclinical testing.

We also create technologies for protein analysis and engineering, including a high-throughput screening platform that enables massively parallel, quantitative biochemical measurements to be performed on millions of protein variants expressed in yeast or bacteria. My presentation will highlight examples of engineered proteins with translational impact, as well as protein engineering applications performed with this new technology platform.

October 27
Ibrahhim I Cisse
RNA Polymerase II cluster dynamics predict mRNA output in living cells
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Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output.

  November 3
Otger Campas
TBA
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TBA

  November 10
NO SEMINAR
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November 17
Peter Lelkes
Modulation of Pluripotent Stem Cell Fate Decision by Microenvironmental Cues
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As part of our ongoing studies into lug tissue engineering we have been focusing on optimizing the efficiency of directed in vitro differentiation of murine embryonic stem cells (mESCs) into lung alveolar epithelial cells. In this presentation I will describe how this differentiative process can be modulated by two microenvironmental cues: oxygen tension and substrate stiffness. Specifically, both these factors, using distinct signaling pathways that involve HIF-1α and Rho/Rock, respectively, independently enhance differentiation of mESCs into definitive endoderm, and subsequently into alveolar epithelium. Augmentation of endodermal differentiation and subsequent alveolar differentiation depend strikingly on the duration of exposure to hypoxia.  Of note is also the marked biphasic nature of the effect of substrate stiffness on endoderm induction. The results of our study will be important in advancing the production of differentiated alveolar cells necessary for cell based therapies of lung diseases and/or for whole lug tissue engineering.

  November 24
NO SEMINAR
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TBA

December 1
Eva Marie Collins
Ripping yourself a new one: Biomechanics of tissue rupture in
regenerating organisms

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Biological tissues are an exciting system to study because they are non-equilibrium materials that consist of self-propelled, interacting agents (cells) and as such exhibit interesting phenomena not observed in passive materials. In my talk I will present our recent work on two
examples of active violent morphological restructuring in biological tissues.

The first study explains how Hydra, a simple freshwater animal, opens its mouth to eat. In contrast to humans and most other animals, Hydra does not have a permanent mouth. Instead, it rips a hole in its skin every time it wants to eat. For a preview, see:
http://shows.howstuffworks.com/now/hydra-mouth-video.htm

The second study explains how freshwater planarians rip themselves apart during asexual reproduction using only substrate adhesion and their own musculature. How this feat can be achieved is a complex biomechanics problem which reportedly already bugged the great Michael Faraday, but has
remained a mystery for centuries.

Each study solves a longstanding puzzle about a fundamental biological phenomenon which remained unsolved due to a lack of experimental tools and quantitative measurements. These examples further illustrate how complex biological phenomena can be described by relatively simple physics and
that our quantitative approach provides new insights into the biological mechanisms underlying these phenomena.

December 8
12PM
Jun Song
Telomere Maintenance in Glioma
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Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, which are fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBMs), harbor highly recurrent TERT promoter mutations specific to two nucleotide positions. I will describe how we have recently identified the functional consequence of these mutations in GBMs to be recruitment of the multimeric GA-binding protein (GABP) transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native E26 transformation-specific motifs critically cooperate with these mutations to activate TERT by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant TERT activation in multiple cancers and provides an opportunity for targeting these highly recurrent non-coding mutations.

December 15
Prashant Mali
Therapeutic Strategies via CRISPR-Cas: new approaches and new challenges
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The recent advent of RNA-guided effectors derived from clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems have dramatically transformed our ability to engineer the genomes of diverse organisms. As unique factors capable of co-localizing RNA, DNA, and protein, tools and techniques based on these are paving the way for unprecedented control over cellular organization, regulation, and behavior. Here I will describe some of our ongoing efforts towards engineering this system for enabling therapeutic applications.

 

January 19
Kimberly Kelly
Hitting the Target: Imaging, Nanotechnology and Drug Delivery in Pancreatic Cancer

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The era of “omics” has ushered in the hope for personalized medicine.  Proteomic and genomic strategies that allow unbiased identification of genes and proteins and their post-transcriptional and -translation modifications are an essential component to successful understanding of disease and the choice of imaging targets.  However, the enormity of the genome and proteome and limitations in data analysis make it difficult to determine the targets that are particularly relevant to human disease and will be good targets for molecular imaging and targeted drug therapies.  Methods are therefore needed that allow rational identification of targets based on function, relevance to disease, and suitability for molecular imaging and therapy.

Through this lecture, we will explore one clinical scenario: pancreatic ductal adenocarcinoma (PDAC) as an application for target identification, imaging and therapeutic agent development. PDAC is among the most lethal of human cancers due to its marked resistance to existing chemo- and radiotherapies.  Unlike a number of other solid tumors, which have robust methods for early detection, there have been no significant improvements in PDAC survival over the past 40 years despite a large number of clinical trials of both conventional and targeted therapies.  Like other solid cancers, early detection that allows complete surgical resection offers the best hope for longer survival, unfortunately, most patients are diagnosed with metastatic disease due to the lack of specific symptoms and absence of suitable biomarkers for early detection.

 

January 26
April Kloxin
TBA

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February 2
12PM
Long Cai
Spatial genomics and single cell lineage dynamics by seqFISH and MEMOIR

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Identifying the spatial organization of tissues at cellular resolution from single cell
gene expression profiles is essential to understanding many biological systems. We have developed an in situ 3D multiplexed imaging method to quantify hundreds of genes with single cell resolution via Sequential barcoded Fluorescence in situ hybridization (seqFISH) (Lubeck et al., 2014). We used seqFISH to identify unique transcriptional states by quantifying and clustering up to 249 genes in 16,958 cells. By visualizing these clustered cells in situ, we identified regions within distinct composition of cells in different transcriptional states. Together, these results demonstrate the power of seqFISH in transcriptional profiling of complex tissues.  Lastly, I will discuss our work in writing lineages and cell event history into genome of cells by CRISPR/Cas9 genome editing and reading out the stored information in single cells by seqFISH. 

  February 9
Andre Fenton
TBA
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February 16
Nandan Nerurkar
Molecular Control of Physical Forces During Morphogenesis of the Vertebrate Gut

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Changes in the shape of a material – be it rubber, concrete, cells, or tissue – requires the action of physical forces. Therefore during embryonic development, the dramatic transformation from a seemingly disorganized mass of cells into the fully patterned adult form necessitates stereotyped regulation of forces at the genetic and molecular level. While great progress has been made in understanding how gene expression and signaling events generate biological pattern, little is known about how molecular cues organize forces to sculpt physical patterns during development. How does the developing embryo ensure that tissues are shaped by the right forces, acting at the right time and location, and with the right orientation and magnitude?  My work begins to address this in two complementary contexts during gastrointestinal morphogenesis in the chick embryo: gut tube formation and intestinal looping. Together these studies demonstrate how secreted signals are converted into tissue-level forces that shape the developing embryo, and yield new insight into important gastrointestinal birth defects. The long-term goal of this work is to provide insight into the fundamental mechanisms of tissue formation, ultimately revealing a molecular-mechanical toolkit of embryonic development that can be redeployed in the context of regenerative medicine and tissue engineering.

  February26
TBA
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March 2
TBA

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  March 9
TBA
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  March 16
TBA
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March 23
TBA

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  March 30
TBA
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April 6
Sindy Tang
TBA

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April 13
Ahmad Khalil
TBA

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April 27
Ali Khademhosseini
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