Linda Griffith, Professor of Biological and Mechanical Engineering

Director, MIT Biotechnology Process Engineering Center
Chair, MIT Biological Engineering Undergraduate Programs Committee

Lorenna Lee-Houghton, PhD Candidate, Biological Engineering
B.S.E. Biomedical and Electrical Engineering, Duke University

An in vitro mouse model of chronic inflammation to study apoptosis in hepatocytes
A link between chronic inflammation and cancer has been established, but the mechanisms of carcinogenesis in inflammatory environments remain poorly understood.  The focus of this work is to elucidate the cell signaling states associated with genotoxicity in hepatocytes under conditions of chronic inflammation by using a set of extracellular cues, both soluble and matrix-related, which can be varied systematically to create a diverse range of intracellular signaling states and phenotypic outcomes.
BE REU Alum: Nidhi Tripathi (Duke)

Ta Hang, PhD Candidate, Biological Engineering
B.S. Bioengineering, U. Minnesota
Coadvisor: Douglas Lauffenburger

Understanding cues and mechanisms to survival of liver sinusoidal endothelial cells and the inflammatory modulation of signaling pathways in angiogenesis.
"Primary liver sinusoidal endothelial cells are notoriously difficult to culturein vitro. My work is focused on trying to parse out the contributions ofcertain cues on the signaling mechanisms for prolonging their cell survival andphenotype. Concomitantly, I am also interested in trying to parse out signalingpathways activated in angiogenesis within the context of inflammation.(iv) Current UROPs: Christopher Cosmides

Miles Miller, Ph.D. Candidate, Biological Engineering
BS, Chemistry, Princeton
Co-Adviser: Douglas Lauffenburger

Understanding how MMP and ADAM activities interact with cell signaling networks to mediate cell migration
Matrix metalloproteinases (MMPs) and A Disintegrin and Metalloproteinases (ADAMs) mediate diverse cellular processes, including extracellular matrix (ECM) degradation and surface-bound growth factor shedding.  We aim to use multivariate protease activity measurements to understand complex networks of extracellular protease activity and how they interact with signaling pathways to affect cell migration, tumor invasion, and establishment of ectopic endometrial lesions in endometriosis.

Caroline Chopko, PhD Candidate, Chemical Engineering
Co-advisor: Paula Hammond, Doug LauffenburgerBS. Chemical Engineering (Mat.Sci. and Bioeng. Minor) Princeton University

Developing a Multiplexed Protease Sensor
My project aims to develop a multiplexed assay to monitor protease activity in long term cell culture.  This experimental tool will be used to assess how perturbations in a single protease can perturb a network and also has applications to developing "signatures" of rare cells in a complex cell mixture.

Jaime Rivera, PhD Candidate, Biological Engineering
B.S., Chem. Eng. and Biology, University of Puerto Rico at Mayaguez

Protein Engineering for Musculoskeletal Regenerative Technologies
This project focuses on new strategies to improve the use of bone marrow-derived mesenchymal stem cells and connective tissue progenitor cells in the operating room for enhancement of bone wound healing. We focus on early stages of cell responses to bone regeneration scaffolds, and are modifying these scaffolds with growth factor and adhesion receptor ligands to enhance selection of cells, and early survival and proliferation following transplantation. Work is done in collaboration with the Armed Forces Institute for Regenerative Medicine.

Edgar Sanchez Palacios, PhD Candidate, Biological Engineering
B.S. Bioengineering, UC Davis

Environmental Cues Regulating Migration of Mesenchymal Stem Cells in Physiological Environments
Mesenchymal stem cells migrate from bone marrow to sites of wound healing and inflammation, and are essential for healing wounds in bone. This project focuses on integration of signaling through EGF receptor family members and adhesion receptors in migration through 3D matrices and in tissue engineering scaffolds.

Walker Inman, PhD Candidate, Mechanical Engineering
B.S., Mech. Eng., Georgia Tech
MS. Mech Eng. MIT

Microscale Perfused 3D Liver for Drug Development
The focus of this project is to development methodologies for analysis of candidate drug toxicity in a 3D liver model designed for use in the pharmaceutical industry. The project encompasses several facets, including the role of interacting cell types, gradients of nutrients, and mechanical stresses on biological responses.

Seymour de Picciotto, Biological Engineering 1st year
MS Swiss Federal Institute, Lausanne, Switzerland in collaboration with Griffith lab at MIT.

Biasing EGF Receptor Dimerizaiton in Mesenchymal Stem Cells
The EGF receptor family plays essential roles in many stages of bone development, homeostasis, and healing. This project focuses using a novel class of engineered bivalent ligands to bias dimerization of EGFR family members. The effects of dimerization are assessed in multiple ways including analysis of receptor activation, downstream signaling, and phenotypic behaviors including survival, growth, and migration.

Courtney Williams, Post-Doctoral Associate
BS, Molecular Biochemistry and Biophysics, Yale University
PhD, Molecular Biology, Princeton University
cmwill@mit.edu

Integration of Gel Matrices into Flow Bioreactors
Hepatocytes in the liver sinusoid integrate a wide array of signals from the extracellular micrenvironment.  My project entails engineering synthetic and semi-synthetic hydrogels to create biologically relevant microenvironments for the maintenance of primary hepatocytes in vitro.

Geeta Mehta, Postdoctoral Associate
Collaboration with the Kamm Lab
BE (Honors), Chemical Engineering, Panjab University (2001)
MS, Chemical Engineering, Michigan State (2004)
PhD, Biomedical Engineering, U Michigan (2008)
gmehta@mit.edu

Physiologically-responsive matrices and microfluidic environments for in vitro tissue engineering
Projects span two areas united by a theme of developing physiologically-responsive matrices for directing dynamic processes in 3D tissue formation in vitro, to enhance models of liver physiology and understand migration of cells in wound healing. In one project, self-assembling peptide hydrogels are modified with ligands for cell adhesion and growth factor receptors, to influence cell proliferation and migration. A related effort emphasizes development of proteolytically-sensitive polymers for analyzing cell migration.

Abigail Oelker, Post-Doctoral Associate
Co-advisor: Paula Hammond
BS, Chemical Engineering, Lehigh University
PhD, Chemistry, Boston University
aoelker@mit.edu

Design and synthesis of 3D microenvironments for mesenchymal stem cell migration 
The mechanisms that guide activation and trafficking of mesenchymal stem cells (MSCs) to sites of inflammation are poorly understood. The goal of my research is to design well-defined scaffolds that support in vitro adhesion, proliferation, and migration of MSCs. The behavior of MSCs in these scaffolds will allow me to elucidate the structural and soluble cues that guide MSC behavior, yielding information that will be relevant for the design of tissue engineering scaffolds and other stem-cell associated therapeutics.

Ajit Dash, Postdoctoral Associate
Collaboration with the Tannenbaum Lab
Degrees from India
PhD, Biological Engineering
drajit@mit.edu

3D In vitro models of idiosyncratic toxicity
A major problem in drug development is failure late in clinical trails due to liver toxicity. My work focuses on building an in vitro model that can be used to test hypotheses about synergies between liver inflammation and drug toxicity, using a microreactor system that captures 3D liver physiology.

Nicole Pfäffle Doyle, Post-Doctoral Associate
Co-mentor: Keith Isaacson, MD Director of Minimally-Invasive Gynecology Surgery, Newton Wellesley Hospital
MD/PhD, Technical University of Munich
NPFAEFFLE@PARTNERS.ORG

A functional assay for initiation of endometriosis lesions from cells in peritoneal fluid.
Endometriosis affects ~10% of women with onset in early reproductive years. In this project, we are characterizing the properties of cells in peritoneal fluid of women with and with out the disease, using a combination of methods including FACS analysis, colony-forming assays, and resistance to pro-death cytokines.

Michael Beste, Post-Doctoral Associate
In collaboration with: Doug Lauffenburger, Keith B. Isaacson

Engineering New Directions in Endometriosis: Endometrial epithelia and stroma in 6-10% of women exhibit reduced hormonal sensitivity, allowing tissue fragments to survive and proliferate following autotransplantation into the peritoneal cavity. Our work aims to understand how cytokine and growth factor signaling in progesterone-resistant endometrium is skewed towards a pro-survival response that protects cells from apoptosis. While many individual pathways have been implicated in persistent survival, we are pursuing network-wide measurements to capture context-specific effects that reveal how cells integrate multiple cues in a complex inflammatory environment. This approach will be applied in comparative model  for healthy and diseased endometrium in order to identify effective strategies to interfere with the lesion formation process in women susceptible to endometriosis. 

Shelly Peyton, Postdoctoral Fellow
Co-mentor: Doug Lauffenburger
BS. Chem. Eng., Northwestern U.
PhD, Chem. Eng., UC Riverside

Mesenchymal Stem Cell Migration in 3-D Synthetic ECM Analogs
Several recent studies highlight the possibility of using multipotent adult bone marrow-derived mesenchymal stem cells (MSCs) for tissue engineering applications, and certain soluble factors (such as EGF) have been identified and characterized for their ability to promote MSC migration; however, much less is known about the role of the 3-D scaffold, designed to mimic the native ECM, in regulating the motility of these stem cells.  I am currently investigating how the physical and chemical properties of a 3-D synthetic ECM analog can regulate the migration and EGF-triggered signaling of adult MSCs.

Major Luis M. Alvarez, PhD
Visiting from: US Army Natick Research Lab
B.S. Engineering, West Point
MS Chemical Engineering, MIT
PhD, Biological Engineering, MIT (2009)

Protein Engineering for Musculoskeletal Regenerative Technologies
We recently developed bivalent ligand dimers that bias homo- and hetero-dimerization in the EGF receptor family, with consequences for downstream signaling and phenotypic behaviors such as cell survival, proliferation, and migration. We also developed approaches to modify the surfaces of bone scaffolds with these ligands in a facile manner. Current efforts focus on applying these technologies for regeneration of musculoskeletal injuries in collaboration with the Armed Forces Institute for Regenerative Medicine.

Steven M. Jay, Postdoctoral Associate
Visiting from: Richard Lee Laboratory, Brigham and Women's Hospital, Cardiovascular Medicine
B.S.. Biological Engineering (with Honors), University of Georgia 2004
Ph.D. Biomedical Engineering, Yale University, 2009

Protein Engineering for Cardiac Regeneration
We aim to engineer proteins to control and exploit signaling pathways for induction of tissue regeneration in the heart.  Molecular biology and biomaterial strategies for intramyocardial delivery of such proteins are also under development.

Rachel Pothier, Technical Assistant
BA Biology, Framingham State 

Liver Tissue Engineering
My work focuses on providing technical support for primary liver cell isolation, characterization and culture in 2D and 3D formats. Muh of my work is in collaboration with the Rusyn lab at UNC and focuses on toxiocology.