Canary Center at Stanford Internship Projects

Faculty Mentor: Zhen Cheng, PhD
Internship Mentor:  Zhen Cheng, PhDHao Chen, PhD, Ning Zhao, Su Hyun Hong, PhD

Internship Positions: 4 positions available, High school or Undergraduates
Type of Laboratory Research: Combination of wet and dry lab

The main objective of Dr. Zhen Cheng's lab is to develop novel molecular imaging probes and techniques for non-invasive detection of cancer and its metastasis at the earliest stage, to cure cancer or transform it into a manageable disease.  Currently, Dr. Zhen Cheng's lab is actively studying several important topics in the cancer molecular imaging field. Especially, near infrared optical imaging is a very promising technology for non-invasively imaging, and Dr. Zhen Cheng's lab focuses on developing novel peptides, small molecules and nanoparticles based molecular probes for targeted tumor imaging. Interns will be involved in development and evaluation of optical probes for cancer diagnosis and image guided surgery. 


Faculty Mentor: Jeremy Dahl, PhD
Internship Mentor: Jeremy Dahl, PhD, Dongwoon Hyun

Internship Positions: 1 position available, Undergraduates only

Type of Laboratory Research: Combination of wet and dry lab

Development of coherence-based ultrasound imaging techniques for molecularimaging. Ultrasound molecular imaging is an attractive modality for early cancer detectionbecause it does not use ionizing radiation, has real-time imaging capabilities, and can beused to target specific cancers.   In ultrasound molecular imaging, gas-filled echogenicmicrobubbles are modified by adding coatings to the microbubble shell that make themfirmly attach to molecular markers.   These gas-filled bubbles act as reflectors of ultrasonic wave to generate high-contrast signals that indicate the location of the molecular marker,and thus the cancer.  Technical challenges remain, however, in the ability to detect thesetargeted microbubbles with ultrasound imaging techniques used to identify thesemicrobubbles.  Microbubbles are sensitive to the amplitude of the ultrasonic pressurewave, and the rate at which they are dissolved or destroyed increases with pressure.  Thus,the pressures required to image the microbubbles must be kept to several orders ofmagnitude below that of conventional diagnostic B-mode to prevent significant loss of themicrobubbles that would provide localization of tumors. The low pressures required forthis type of imaging creates a low signal-to-noise ratio, because the echoes are notsignificantly greater than the ultrasound system’s thermal noise. While a largeconcentration of microbubbles generates sufficient reflections to overcome noise, a lowconcentration, such as the case of targeted microbubbles and small cancers, can beoverwhelmed by thermal or other sources of noise.  In this project, we will continue todevelop a real-time imaging modality, based on the coherence of microbubble signals, toimprove the sensitivity of ultrasound molecular imaging.  Tasks of the project will involveprogramming in Matlab and/or CUDA, imaging and data acquisition with ultrasound, andmicrobubble creation.  Knowledge of medical imaging or ultrasound physics and familiaritywith Fourier Transforms and basic signal & systems concepts will be helpful.


Faculty Mentor: Utkan Demirci, PhD
Internship Mentor: Murat Baday

Internship Positions: 1 positions available, Undergraduates only

Type of Laboratory Research: Combination of wet and dry lab

The laboratory of Dr. Demirci focuses on creating micro- and nano-scale technologies to solve real world problems in medicine. An Intern is needed in developing cancer diagnostic tools through the understanding of mechanical tools. We are establishing a 3-D high-resolution traction force microscopy platform integrated with 3-D microreology measurement of tissues through fluorescent microscopy for cancer mechanics studies. This will not only be replacement for AFM force-distance measurements, but also provide real-time measurement of ECM stiffness while imaging cell phenotypic changes of cells under varying conditions. We are planning to correlate the cells force generation with protein and RNA expression of certain EMT and stem cell markers under different surface stiffness and ECM conditions. By studying mechano-transduction and pathways associated it will provide new approaches for drug development to slow down the cancer progression. The intern will be involved in tissue culture, imaging experiments, and analyzing data. All these will provide extensive knowledge of cancer biology and handling cancer tissues as well as interpreting and analyzing imaging of cancer tissues.


Faculty Mentor: Utkan Demirci, PhD
Internship Mentor: Thiruppathiraja Chinnasamy

Internship Positions: 1 position available, Undergraduates only

Type of Laboratory Research: Combination of wet and dry lab

The title of the project we will be working on is “Design and developing a microfluidic device based differential cell manipulation for clinical diagnostic application”.


Faculty Mentor: Utkan Demirci, PhD
Internship Mentor: Vigneshwaran Mani

Internship Positions: 1 position available, Undergraduates only

Type of Laboratory Research: Combination of wet and dry lab

Development of integrated microchip ELISA for rapid detection of cardiac and infectious disease diagnostics. Specifically, we are interested in integrated test devices for rapid cardiac biomarker detection for acute coronary syndrome diagnostics. The developed device will be fast, accurate, and could potentially be used in point-of-care settings for rapid acute coronary syndrome diagnostics from whole blood. 


Faculty Mentor: H. Tom Soh, PhD
Internship Mentors: Gurpreet Sekhon, PhD and Diana Wu

Internship Positions: 2 positions available, Undergraduates only
Type of Laboratory Research: Wet lab

The Soh Laboratory is interested in developing biosensor discovery technologies capable ofgenerating highly accurate and sensitive biosensors for simultaneous detection andreporting of disease biomarkers. As current technologies typically require long andcumbersome rational design schemes that often produce less than ideal sensitivity/accuracy, our approach streamlines this workflow by displaying nucleic acidcandidate libraries on bead particles and sorting the resulting populations with high-throughput FACS instrumentation.  The resulting biosensors isolated not only bind theircorresponding biomarkers with high affinity and specificity, but also simultaneously reportthe binding event through integrated signaling systems.   Thus we can produce highlyeffective, low-cost biosensor constructs that are directly translatable to a point-of-careclinical setting, as minimal post-discovery intervention is needed. To assist with this project, we are seeking a highly motivated and enthusiasticundergraduate research intern with a background in a relevant physical or life sciencesdiscipline.  The student will be exposed to wide spectrum of laboratory techniques rangingfrom bench work pipetting to assisting in running FACS instrumentation.  The student willgain knowledge on the fundamentals of nucleic acid and protein synthesis and chemicalmodification, solid-phase bio-conjugation chemistries, and working with DNA librariestailored for directed evolution.  Students with chemistry and/or biology lab experiencewould be preferred.


Faculty Mentor: Sanjiv Sam Gambhir, MD, PhD
Internship Mentor: Edwin Chang, PhD

Internship Positions: 1 position available, High school or undergraduate
Type of Laboratory Research: Wet lab

Glioblastomas (GBM) are an exceptionally aggressive class of brain cancer.  Unfortunately, it is also the main type of primary tumor that patients suffering from brain cancer will encounter.  GBM is not only extremely proliferative but it 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.  Since, GBM lines grow as suspension cell cultures (i.e. the cells float and grow in liquid suspension as opposed to sticking to the bottom of the plate); the intern will learn both adherent and 3-dimensional cell cultures for several glioblastoma lines.  To monitor the therapeutic impact of our screened drugs, standardized bioassays for cellular activity (cell counts, alamar blue and MTT proliferation assays, neurospheres size distribution, bioluminescence activity) will be introduced and mastered.  The intern will familiarize herself/himself with standardized equipment for the application of alternating electric fields on glioma-derived cell cultures.  If time permits, the intern will be shown the fundamentals of preclinical model development.  The models will then be employed to validate drugs that have passed the initial screen from cellular culture. Such investigations will also introduce the intern to established bioluminescence assays of cancer cell growth and development.  


Faculty Mentor: Sanjiv Sam Gambhir, MD, PhD
Internship Mentor: Sharon Hori, PhD

Internship Positions: 1 position available, Undergraduates only
Type of Laboratory Research: Mixture of wet and dry lab

Most cancers can be more effectively treated if they are discovered early. Dr. 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 and study novel strategies to detect small, early-stage cancers from a routine blood sample. This involves learning and conducting wetlab experiments in molecular and cell biology, with the option to integrate experimental data with computational modeling techniques to study the relationship between a growing tumor and the amount of biomarker it secretes.

The internship applicant should be a highly-motivated undergraduate with a basic background in molecular/cellular biology and/or mathematics (single-variable calculus required), 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, 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.


Faculty Mentor: Sanjiv Sam Gambhir, MD, PhD
Internship Mentor:  Arut Natarajan, PhD

Internship Positions: 2 positions available, Undergraduates only
Type of Laboratory Research: Wet lab

Our goal is to select, develop, and optimize protein binders to target immune check points/cancer biomarkers from the FN3 protein library. The best pM candidate binder will be further studied for pre-clinical imaging and translational research. 


Faculty Mentor: Parag Mallick, PhD

Internship Positions: 4 positions available, High school or undergraduate
Type of Laboratory Research: Dry lab

The emergence of high-throughput experimental measurements of the genome, transcriptome, proteome, etc. has created an explosion of basic biological data. However, these data have not led to a corresponding explosion in new cancer therapeutics. Generally speaking, the drug pipelines have slowed.  We believe that these failures result from three factors: 1) a gross over-simplification of how messages are passed within cells and accordingly how cells make decisions about how to respond to diverse perturbations (i.e. grow faster, grow slower, move, die); 2) the inability of researchers to understand or describe the consequences of patient-to-patient variation on cell decision making and ; 3) the complex and non-linear dynamics at work in cell’s regulatory processes.  

These issues have been highlighted recently with a number of publications showing massive discordance between a gene’s transcript and protein levels.  Though startling to the community, these results are actually unsurprising given the diverse processes regulating a gene’s transcript and protein levels.

To accelerate the extraction of knowledge from vast datasets and enable them to be better leveraged we are looking to develop an web visualization interface coupled to a back-end simulation engine to enable researchers to 1) visualize the complex multi-layered relationships between genes, transcripts, proteins and metabolites; 2) visualize variations of a system’s components throughout the cellular network and ; 3) perform and visualize dynamic simulations to observe the possible consequences of cellular perturbations and therapeutic interventions. 


Faculty Mentor: Ramasamy Paulmurugan, PhD
Internship Mentors: Ramasamy Paulmurugan, Thllai Veerapazham

Internship Positions: 2 positions available, Undergraduates only
Type of Laboratory Research: Mixture of wet and dry lab

Cellular Pathway Imaging Laboratory (CPIL)

The main focus of our laboratory 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.   

 

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. Therefore, histone methylation marks are identified as promising therapeutic targets. However, simple and sensitive tools that monitor these changes are not prevalent. We developed molecular imaging sensors for the real-time monitoring of H3K9me/chromodomain and H3K27me/chromodomain interactions in cells and small animals. Imaging sensors for other important methylation marks are under-evaluation. These imaging sensors are essential tools for studying the changes in histone methylation during disease development, and for screening small molecule drugs that modulate histone methylation patterns in cancer cells.

Developing genetically encoded Molecular sensors for Imaging Protein-Protein Interactions and Protein folding

We extensively use the developed split-reporter protein complementation systems (Firefly, Renilla, Gaussia, GFP, and mRFP) to monitor protein-protein interactions and protein folding. Using the established reporter proteins, we designed genetically encoded molecular imaging sensors for studying histone methylation, p53-protein folding, p53-sumoylation, ligand-induced changes in estrogen receptor folding, NRF2-Keap1 interactions, and down-stream response of major cellular pathways such as NFκB, and NQO1.

 

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 its dysregulation is implicated with breast, ovarian, and endometrial cancers. We developed firefly luciferase reporter complementation sensor for imaging ligand-induced conformational changes in ERα. We also developed a transgenic mouse model expressing this complementation sensor. We used 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. Currently using this complementation sensors and transgenic mouse, we extend our studies to assess the role of ER-β in 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.

Screening Small Molecules modulating NRF2 and NFkB signaling pathways for developing combination therapy to treat cancers

We are also exploring the role of Nrf2-pathway for acquired chemoresistance in cancer therapy. Overexpression of NRF2 protein in cancer cells resulting in chemo- and/or radioresistance. This necessitates understanding of Nrf2-regulation, and identification of Nrf2 activators/inhibitors sensitizing cancer cells to improve chemotherapy. We developed complementation sensor to study NRF2-Keap1 interactions, and ARE-FLuc sensor to study the activation of antioxidant responsive genes, for screening small molecule drugs that can modulate NRF2 pathway. NFkB signaling pathway is another major signaling network regulating immune response to various infections. Dys-regulation of NFkB proteins implicated in major diseases including cancer. We developed an imaging sensor to monitor the activation of NFkB genes in response various stress signals. We apply these imaging sensors to screen small molecules that simultaneously modulate both Nrf2 and NFkB signaling to improve cancer therapy.

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

Small molecule chemotherapeutic agents lead 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 develop PLGA nanoparticles for delivering the 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 investigate the possible association of microRNAs with breast cancer development and tamoxifen resistance in particular. Additionally, we study the therapeutic utility of PLGA-loaded sense- and antisense- microRNAs to curtail the metastasis of breast cancer. 


Faculty Mentor: Sharon Pitteri, PhD

Internship Positions: 2 positions available, Undergraduates only
Type of Laboratory Research: Wet lab

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 two 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. Undergraduate level coursework in chemistry and/or biology are required. Preference given to Stanford students who wish to continue research during the school year. This internship is a full time (8 hours per day), eight week minimum commitment.


Faculty Mentor: H. Tom Soh, PhD

Internship Positions: 1 position available, Undergraduates only

Type of Laboratory Research: Wet lab

Evolution only requires three basic elements: mutation (for diversity), selection (for function), and amplification (for making more of the winning species). In our work, we use these evolutionary principles to synthesize new materials that do not exist in nature but can perform complex and useful functions. In particular, we are focused on evolving nucleic-acid materials (called “aptamers") that can perform molecular recognition, because these materials offer new avenues for improving molecular diagnostics and targeted therapies.  The students will be involved in discovering new aptamers proteins and small molecules using high-throughput technologies developed by our laboratory.


Faculty Mentor: Tanya Stoyanova, PhD

Internship Positions: 1 positions available, Undergraduates only

Type of Laboratory Research: Wet lab

Our research focuses on understanding fundamental molecular mechanisms underlying cancer development. Currently, we study signaling cascades initiated by cell surface receptors. We are interested in how these receptors signal to drive prostate cancer initiation and how they regulate the transition from indolent to aggressive disease. The long term goal of our laboratory is to improve the stratification of indolent from aggressive prostate cancer and aid the development of better therapeutic strategies for the advanced disease.

Additionally, we are interested in understanding molecular mechanism that govern the self-renewal activity of adult stem cells and cancer stem cells. We use molecular biology techniques, cell culture based adult stem cell assay and in vivo tissue regeneration models of cancer.


Faculty Mentor: Juergen K. Willmann, MD
Internship Mentors: Ahmed El Kaffas, PhD, Alireza Akhbardeh

Internship Positions: 1 positions available, Undergraduates only
Type of Laboratory Research: Dry lab

Computer-aided-diagnosis system Development using dynamic contrast-enhanced ultrasound and machine learning techniques.

Currently there is a critical need in developing cancer-imaging methods for treatment monitoring and to assess if the response to therapy works. Dynamic contrast material–enhanced (DCE) imaging techniques such as DCE-computed tomographic (DCE-CT) and DCE-magnetic resonance (DCE-MR) imaging were shown to be effective in detecting changes in tumor perfusion before there were changes in lesion size. However, there is limited access to MR and CT machines and the examination is relatively expensive. As an alternative 3D+time dynamic contrast-enhanced ultrasound (DCE-US) imaging is used to evaluate response to treatment in organs that are accessible for US imaging.

This project is a computer-aided-diagnosis system development using dynamic contrast-enhanced ultrasound and machine learning techniques to quantify dilution for ultrasound contrast agents in tumors by extracting some physiologically meaningful hemodynamic parameters from dilution profile in tumors and we will use them as inputs to machine learning algorithms for fusing extracted parameters and predicting treatment effectiveness more efficiently. As a part of this project, the image processing and optimization (curve fitting) techniques will be used as well.

The candidate should have background in electrical Eng., biomedical

Eng., computer science, or similar; sufficient programming skills in Matlab, Python and C++ is needed.