Canary CREST Program Projects

PI: Zhen Cheng, PhD
Mentor:  Hao Chen, PhD, Ning Zhao, Chunrong Qu

Positions available: Up to 3 students
Type of Research: Combination of wet and dry lab

Project or lab description: 

Students will work on the development of optical probes with long emission wavelengths for bioimaging purposes.

The overall objective of my laboratory is to develop novel molecular imaging probes and techniques for non-invasive detection of cancer and its metastasis at the earliest stage, so that cancer can be cured or transformed into a chronic, manageable disease. The techniques developed in my research will allow a close examination of the molecular, metabolic and physiological characteristics of cancers and their responses to therapy. In order to achieve this goal, my lab is aimed to identify novel cancer biomarkers with significant clinical relevance, develop new chemistry for probes preparation, and validate new strategies for probes high-throughput screening.    


PIJeremy Dahl, PhD
Mentor: Jeremy Dahl, PhD and Dongwoon Hyun

Positions available: 1 student
Type of Research: Combination of wet and dry lab

Project or lab description:

In our lab, we are investigating methods to improve ultrasound molecular imaging (USMI). In USMI, gas-filled microbubbles are coated with molecules that attach firmly to specific biomarkers. Once attached, the microbubbles reflect ultrasound pressure waves strongly, indicating the presence of the biomarker. By using microbubbles targeted to biomarkers associated with cancer, USMI can be used for early cancer detection. However, the microbubbles are sensitive to the amplitude of the ultrasonic pressure wave and require pulses that are several orders of magnitude weaker than those used in diagnostic imaging. The low pressures required for USMI result in poor signal-to-noise ratio, making it difficult to detect low concentrations of microbubbles, as is often encountered in USMI. In this project, we will develop improved ultrasound beamforming algorithms to better detect and localize microbubbles in real-time. Tasks of the project will involve programming in MATLAB and/or CUDA, imaging and acquiring data with ultrasound, and synthesizing microbubbles. Knowledge of medical imaging or ultrasound physics and familiarity with Fourier transforms and basic signals and systems concepts will be helpful.


PI: Utkan Demirci, PhD
Mentor: Fatih Inci, PhD, Loza Tadesse, Naside Gozde Durmus, PhD, Memet Ozen, PhD, Shreya Deshmukh

Positions available: Up to 4 students
Type of Research: Combination of wet and dry lab

Project or lab description:

Our laboratory focuses on creating micro and nano scale technologies to solve real world problems in medicine. The students will be involved in Cell sorting, device fabrication, imaging experiments, and analyzing data.


PI: Sanjiv Sam Gambhir, MD, PhD
Mentor: Edwin Chang, PhD

Positions available: 1 student
Type of Research: Wet lab

Project or lab description:

Glioblastoma (GBM) is an exceptionally aggressive and chief class of brain cancer.  GBM is not only extremely proliferative but is genomically and phenotypically heterogeneous.  The diversity of subgroups within a GBM makes therapy difficult and consequently, there are few therapeutic and diagnostic tools that can be used to combat the disease.  In this internship, the intern will participate in finding such new tools by screening promising drugs against glioblastoma cell cultures of human origin.  Once we have identified the leaders, we will then validate them in preclinical models of human GBM.  In addition to finding chemotherapeutic targets against GBM the intern will also explore the feasibility of combating GBM with a novel, physico-chemical therapy that recently received approval for clinical use from the Food and Drug Administration (FDA), namely the application of exogenous, alternating fields or Tumor Treating Fields (TTFields).  Part of the internship will involve the exploration of TTField therapy in combination with novel chemotherapies against GBM.

            The internship will expose the individual to a number of techniques that are relevant and necessary for the fields of biomedical and molecular imaging research.  The intern will learn both adherent and 3-dimensional cell cultures for several glioblastoma lines.  Standardized bioassays for cellular activity (cell counts, alamar blue and MTT proliferation assays, neurospheres size distribution, bioluminescence activity) will be introduced.  The intern will familiarize herself/himself with equipment for the application of alternating electric fields on glioma-derived cell cultures.  If time permits, the intern will be shown fundamentals of preclinical model development.  Such investigations will also introduce the intern to established bioluminescence assays of cancer cell growth and development.


PI: Sanjiv Sam Gambhir, MD, PhD
Mentor: Frezghi Habte, PhD

Positions available: Up to 2 students
Type of Research: Dry lab

Project or lab description:

Canary Center Preclinical Imaging Laboratory is a shared service center Imaging facility formed to provide resources for the application and advancement of technologies for in-vivo biological assessment and imaging in animal models. Its mission is to develop an infrastructure, strategies, expertise and tools to perform multimodality in vivo imaging primarily for preclinical research. The facility provides centralized shared instrumentation and software for in vivo imaging.

Ongoing research projects of the facility focus on the development tools and methods for advanced image quantitation. It is understood that quantitative image analysis has superior advantage in characterizing biological processes more objectively compared to a simple qualitative analysis. However, due to the complexity of the imaging instrument and associated analysis tools, there is still significant variability in quantitative imaging, which makes the development of standardized methods difficult that requires further development. Under this specific project, we will assess exiting overall image analysis tools and methods, and develop new imaging strategies and/or analysis tools that improve the accuracy and efficiency of image quantification techniques. The task of the project will require an interest and basic knowledge of molecular biology, the physics of medical imaging and programming preferably in Matlab and/or C++, and 3D printing experience. 


PI: Sanjiv Sam Gambhir, MD, PhD
Mentor: Sharon Hori, PhD

Positions available: Up to 2 students
Type of Research: Combination of wet and dry lab

Project or lab description:

Most cancers can be more effectively treated if they are discovered early. Dr. Sharon Hori is studying the detectability of early-stage cancers using secreted cancer-specific biomarkers - proteins or molecules released from cancer cells into the blood. The purpose of this internship is to develop innovative strategies to detect small, early-stage cancers from a routine blood sample. This involves learning how to design and conduct molecular and cellular biology experiments, utilize novel molecular imaging techniques, and integrate these experimental results with computational modeling techniques to study the relationship between a growing tumor and the amount of biomarker it secretes. Cancers of the breast, ovary, lung, and pancreas will be the primary focus.

The internship applicant should be a highly-motivated undergraduate with a basic background in molecular/cellular biology and/or mathematics (single-variable calculus), and have a strong desire to learn and integrate biological and computational modeling techniques. Computer programming and mathematical modeling skills are preferred but not required. The intern will have the opportunity to learn how to culture cancer cells, treat cancer cells with chemotherapeutic drugs, perform assays to assess cell viability and measure secreted biomarker levels, image cells using fluorescence and bioluminescence techniques, study cell properties using flow cytometry, develop basic mathematical/computational models for tumor growth and biomarker secretion, and/or use mathematical modeling approaches to study or make predictions about cancer state. This summer internship will provide a unique opportunity to gain hands-on experience in biological and computational research, and is ideal for students interested in molecular/cellular biology, cancer research, medicine, computational and systems biology, biomedical engineering and related fields. Minimum 40 hr/week required.


PI: Sanjiv Sam Gambhir, MD, PhD
Mentor:  Johannes Reiter, PhD

Positions available: 1 student
Type of Research: Dry lab

Project or lab description:

I develop computational and mathematical models to understand the dynamics of biological processes, in particular those relevant during the evolution, spread and treatment of cancer. My research mostly focuses on questions related to tumor progression, metastasis and the evolution of resistance. During this summer internship, the student will work on utilizing cancer phylogenies to forecast tumor evolution.


PI: Olivier Gevaert, PhD
Mentor:  Olivier Gevaert, PhD

Positions available: Up to 2 students
Type of Research: Dry lab

Project or lab description:

Students will work on developing computational models for multi-scale modeling of cancer.

Our lab focuses on multi-scale data fusion in oncology: the development of machine learning methods for biomedical decision support using multi-scale biomedical data. Previously we pioneered data fusion work using Bayesian and kernel methods studying breast and ovarian cancer. Subsequent work concerned the development of methods for multi-omics data fusion. This resulted in the development of MethylMix, to identify differentially methylated genes, and AMARETTO, a computational method to integrate DNA methylation, copy number and gene expression data to identify cancer modules. Additionally, we focus on linking molecular data with cellular and tissue-level phenotypes. This led to key contributions in the field of imaging genomics/radiogenomics involving work in lung cancer and brain tumors. Our work in imaging genomics is focused on developing a framework for non-invasive personalized medicine. 


PI: Sanjay V. Malhotra, PhD, FRSC

Mentor: Angel Resendez, PhD

Positions available: Up to 2 students
Type of Research: Wet lab

Project or lab description:

Our lab is developing diagnostic techniques for the assessment of gastrointestinal (GI) health. We are working on development of boronic acid-based fluorescent sensors and fluorosugar-based MRI Probes for the early detection of GI diseases.

It is hypothesized that drastic changes in permeability is an indicator of early onset of GI diseases, such as chronic inflammatory bowel disease. GI permeability can be assessed non-invasively by analyzing saccharide markers in urine such as sucrose for upper GI permeability, lactulose and mannitol for small intestine permeability and the synthetic sweetener sucralose for colon. Current methods for analyzing these markers require expensive and time consuming instrumentation such as HPLC and LC/MS.  We are developing a new fluorescent-based modular two-component sensing system comprised of the anionic fluorescent dye, and a boronic acid appended viologen that acts dually as a quencher and receptor. These new cost-effective fluorescent sensors will be used to non-invasively characterize GI permeability that would allow early detection of maladies that affect the GI barrier. 

Another currently used clinical methodologies for the detection of GI diseases involve invasive methods such as endoscopy or colonoscopy. Magnetic Resonance Imaging (MRI) of the GI tract using 19F probes has become an important non-invasive tool for diagnosis of GI diseases.  Due to the abundance of the 19F nucleus and similar resonant frequency, i.e. 94% of that of 1H, there have been significant interests in developing fluorine containing molecules as contrast agents in clinical settings. We are developing new fluorosugars that would allow real-time imaging and quantification of intestinal permeability by MRI. Our lab is actively working on design and synthesis of a small library of fluorosugars to be tested for optimal permeability measurements in vitro using the human colon carcinoma cancer cells.


PI: Sanjay V. Malhotra, PhD, FRSC

Mentor: Vineet Kumar, PhD

Positions available: Up to 2 students
Type of Research: Combination or wet and dry lab

Project or lab description:

Students will work on the synthesis of novel small molecules to probe biological targets. Working closely with senior scientists, students will also get training in running biological assays to develop application of small molecules in drug discovery and development. 


PI: Sharon Pitteri, PhD

Mentor: Sharon Pitteri, PhD

Positions available: Up to 3 students
Type of Research: Wet lab

Project or lab description:

The Pitteri Laboratory is focused on the discovery and validation of proteins and other types of molecules in the blood that can be used as indicators of risk, diagnosis, progression, and recurrence of cancer. We specialize in molecular analysis of clinical and biological samples to detect cancer and understand biology. We utilize state-of-the art technologies including liquid chromatography and mass spectrometry to identify, quantify, and characterize proteins and other molecules of interest
We are looking for 1-3 highly motivated undergraduate students looking for an internship to work on a summer research project focused on cancer early detection. The internship is well-suited for students with interests in chemistry, biochemistry, biology, applied physical science, and/or medical research. You will gain hands-on experience with biochemistry and analytical chemistry techniques, and data analysis. Possible projects include analysis of clinical samples and/or cancer cell lines.  A positive attitude, willingness to learn and contribute, and meticulous attention to details are a must. 


PI: H. Tom Soh, PhD

Mentor: Dan Mamerow

Positions available: 1 student

Type of Laboratory Research: Combination of wet and dry lab

We are developing several very sensitive protein detection techniques that can be used in both clinical settings (e.g. measuring many biomarkers at the same time from a small volume of blood) or in research applications (e.g. measuring the proteome of a single cell to determine cellular heterogeneity that is hidden from bulk measurements). We are in active collaboration with several other departments on campus to translate our platforms for clinically relevant demonstration for the early detection of cardiovascular biomarkers as well as infectious disease biomarkers.


PI: H. Tom Soh, PhD

Mentor: Alex Yoshikawa

Positions available: 1 student

Type of Laboratory Research: Wet lab

Project or lab description:

Sugar polymers, known as glycans, are attached to proteins and lipids through a process known as glycosylation. Changes in the expression of glycans are key hallmarks of many human diseases, such as cancer. However glycans remain difficult to study and target therapeutically, largely because of the lack of affinity reagents that can specifically recognize and bind glycan structures. In this project we will be creating a class of affinity reagents known as XNA aptamers that can bind glycans with great specificity. XNA aptamers are nucleic acid based probes which contain unnatural chemical modifications and can bind to targets, such as proteins and small molecules. The XNA aptamers created in this project will have use as cancer therapeutics and as biosensors to detect specific disease states. 


PI: Tanya Stoyanova, PhD

Mentor:  Tanya Stoyanova, PhD

Positions available: Up to 2 students

Type of Laboratory Research: Wet lab

Project or lab description:

We focus on understanding molecular mechanisms underlying cancer development. We are particularly interested in signaling cascades initiated by cell surface receptors and their use as biomarkers for stratification of indolent from aggressive prostate cancer and therapeutic targets for the advanced disease.


PI: Juergen K. Willmann, MD
Mentor: Lotfi Abou-Elkacem, PhD

Positions available: 1 student
Type of Research: Wet lab

Project or lab description:

The Translational Molecular Imaging Laboratory (TMIL)/Willmann Lab, within the Canary Center, is focused on the development and clinical translation of novel molecular and functional imaging biomarkers with special focus on imaging pancreatic and breast cancer.
We are looking for a highly motivated individual to multitask and perform interdisciplinary research projects using protein engineering to develop next-generation molecularly-targeted ultrasound contrast agents for ultrasound molecular imaging. The successful applicant will play important roles in all stages of investigation including: experimental design, protein engineering using yeast display and biochemistry techniques, analytical measurements, and data analysis/interpretation.    


PI: Juergen K. Willmann, MD
Mentor: Ahmed El Kaffas, PhD

Positions available: Up to 2 students
Type of Research: Dry lab

Project or lab description:

Development of Quantitative Ultrasound Methods

The Translational Molecular Imaging Laboratory seeks candidates interested in ultrasound image processing and quantification methods. This is an opportunity to be exposed to analysis, algorithm development and validation of medical imaging biomarkers, and to potentially work directly with clinicians and researchers in gathering data. Candidates will be with 1-2 postdocs and a principle investigator (clinician/scientist) to explore image quantification methodologies in the context of ultrasound imaging, and to carryout experimental work to validate these parameters. The candidate will first be exposed to a variety of activities in the lab and subsequently be given an opportunity to carryout a specific project from start to end with guidance.

Previous Matlab and/or Python experience, specifically in the context of image processing, is an asset. The following list of other specific experiences are assets:

- Experience with bash scripting, and working with NIFTI data and associated toolboxes

- Ultrasound research and/or imaging

- Machine learning and statistical models

- Open CV or other programing languages for image processing

About the Lab: The Translational Molecular Imaging Laboratory focuses on the development and clinical translation of new functional and molecular imaging methods with special focus on ultrasound imaging and biomarker extraction.


PI: Juergen K. Willmann, MD
Mentor: Katheryne Wilson, PhD

Positions available: 1 student
Type of Research: Wet lab

Project or lab description:

This project will involve the development of novel, protein and dye based contrast agents for use with ultrasound, photoacoustic, and fluorescence molecular imaging techniques for early cancer detection. A majority of the research will involving learning extensive wet lab chemistry and biology techniques.


PI: Ramasamy Paulmurugan, PhD
Mentor: Ramasamy Paulmurugan, PhD

Positions available: Up to 3 students
Type of Research: Combination of wet and dry lab

Project or lab description:

The main focus of our laboratory, the Cellular Pathway Imaging Laboratory (CPIL) is to develop in vivo molecular imaging strategies for studying cellular signal transduction networks and to develop promising new therapeutics for treating cancers (Breast cancer, Hepatocellular carcinoma, and Glioma) which are aggressive and resistant to drugs. Below are examples of projects students may work on:

Imaging Epigenetic changes in Cancer cells and Small animals

We are studying the epigenetic changes, such as histone methylation and protein sumoylations that control the normal cellular functions and at different pathological conditions, using optical imaging modality. Histone methylation marks are altered in the pathogenesis of major diseases including cancer. However, simple and sensitive tools that monitor these changes are not prevalent. We are developing molecular imaging sensors for the real-time monitoring of histone methylation marks in cells and small animals.

Imaging BPA induced changes in Estrogen Receptor signaling and the associated oncogenesis in transgenic animals

Estrogen receptors (ER) are the major cell growth and development regulators, and their dysregulation is implicated with breast, ovarian, and endometrial cancers. We are developing firefly luciferase reporter complementation sensors for imaging ligand-induced conformational changes in ERα. We are also developing a transgenic mouse model expressing this complementation sensor. We are using this transgenic mouse model to study the Bisphenol A (xenoestogen) induced changes in ER-signaling and oncogenesis. This transgenic mouse model can also be used for screening novel ligands to treat tamoxifen-resistant breast cancer sub-types. Using complementation sensors and transgenic mouse models, we are extending our studies to assess the role of ER-β in the pathogenesis of breast cancer. We also focus on estrogen independent molecular mechanisms involved in the development, progression, and invasiveness of breast cancers that are negative for ER-a expression.

Developing microRNA therapy for cancers (Breast cancer, Hepato-cellular carcinoma, and Brain Cancer)

Small molecule chemotherapeutic agents lead to non-targeted cytotoxicity when used for cancer treatment. Further, targeted deliveries of therapeutic agents minimize the optimum concentrations of drugs needed to treat cancer. We are developing PLGA nanoparticles for delivering small molecule drugs like tamoxifen, Gemcitabine, antisense-microRNAs, and therapeutic DNAs. MicroRNAs play critical role in the molecular mechanisms responsible for cancer development and drug resistance. We are investigating the possible association of microRNAs with breast cancer development and tamoxifen resistance in particular. Additionally, we are studying the therapeutic utility of PLGA-loaded sense- and antisense- microRNAs to curtail the metastasis of breast cancer.