Summer Undergraduate Research Program
Faculty Project Proposal Submission 2015
Faculty Name: Professor Deborah Dean, MD, MPH
Faculty Email: ddean@chori.org
Phone Number: 510-450-7655
Department/Organization Affiliation:
1) Center for Immunobiology and Vaccine Development, Children’s Hospital Oakland
Research Institute;
2) Director, Children’s Global Health Initiative, Children’s Hospital Oakland Research
Institute;
3) Faculty, UCSF/UCB Joint Graduate Program in Bioengineering
Preferred Method of Contact: email
FOUR PROJECTS AVAILABLE
1.) Project Name(s): Investigate intracellular metabolism of Chlamydia trachomatis and
other Chlamydiaceae species of human disease importance for detecting drug targets
and developing a rational vaccine.
General Topic (keywords): Chlamydia trachomatis, ex vivo tissue, pathogenesis, tissue
engineering, metabolism
Project Description(s): Chlamydia trachomatis (Ct) is an obligate intracellular human
pathogen that multiplies within a parasitophorous vacuole called an inclusion. Ct is the
leading bacterial cause of STDs worldwide with over 100 million cases occurring
annually according to the World Health Organization. Our research identified the first
host proteins that are translocated from the cytoplasm into the inclusion. These proteins
likely support remodeling and scavenging of host lipids into bacterial-specific moieties
essential to Ct growth. We are in the process of further investigating the metabolics of
intracellular Ct infections using established and primary human cervical and endometrial
cells. The latter will more closely mirror what happens in vivo compared to knowledge
that has been gained using only established cell lines or the mouse model of genital tract
infections. Our studies may lead to novel data to develop new drug targets and a rational
vaccine to prevent Ct infections.
Desired Skills or Experience: Undergrad interested in a multidimentional and fulfilling
lab experience – no prior experience required although some courses in molecular
biology and/or genetics would be helpful.
Time Commitment: Full time in summer and then part time during the academic year
for those students interested in continuing; the project could become a senior thesis.
Preferred Starting Date: Late May
______________________________
2.) PROJECT NAME: Genomics and pathogenesis of Chlamydia trachomatis sexually
transmitted and ocular infections.
General Topic (keywords): Chlamydia trachomatis, pathogenesis, host genetic
susceptibility, mucosal immunity, strain typing
Project Description(s): Chlamydia trachomatis (CT) is the leading cause of bacterial
sexually transmitted infections (STIs) and preventable blindness worldwide. Over 9
million people develop chlamydia STIs each year in the US with untold numbers among
ocular trachoma patients in developing countries. Trachoma is a chronic ocular infection
caused by CT. The majority of infections are asymptomatic in both men and women and
can result in the severe complications of pelvic inflammatory disease, infertility, ectopic
pregnancy and chronic pelvic pain or blindness. Recurrence likely results from persistent
infections and also from reinfection. Disease progression is likely immune based and
may be related to host genetic factors. Very little is known about the genomic diversity of
CT strains, host immune responses or host genetic susceptibility to inflammation and
disease related to CT infection. We will evaluate cervical mucosal immunity against
many CT proteins, single nucleotide polymorphisms (SNP) in inflammatory genes and
HLA types among patients with and without disease along with genomic/genetic factors
in CT that may play a role in disease outcome. In addition, we will type CT using a multilocus sequence typing scheme referred to as MLST. In this way, we will develop a better
understanding of the host-pathogen interrelationship and disease pathogenesis for
chlamydial STIs. We will study different global patient populations.
Desired Skills or Experience: Undergrad interested in a multidimentional and fulfilling
lab experience – no prior experience required although some courses in molecular
biology and/or genetics would be helpful.
Time Commitment: Full time in summer and then part time during the academic year
for those students interested in continuing; the project could become a senior thesis.
Preferred Starting Date: Late May
_______________________
3) Project Name(s): Protection from Chlamydia trachomatis sexually transmitted
infections using a novel vaccine.
General Topic (Keywords): Chlamydia trachomatis, vaccine development, vaccine
testing, immune response, sexually transmitted infections
Project Description(s): Prevention of Chlamydia trachomatis (CT) infection represents
a critical unmet medical need. CT causes blinding trachoma, infertility, ectopic
pregnancy and is an important cofactor in cervical cancer and HIV transmission. CT is
the leading bacterial sexually transmitted infection (STI) worldwide. Previous vaccination
efforts have been unsuccessful. Yet, recent research suggests that induction of both
humoral and cellular immune responses are required for protection from infection. Our
research has identified specific CT antigens that we integrated into a non-toxic form of
Pseudomonas aeruginosa exotoxin A (ntPE). We have shown that one construct (ntPE1)
elicits both systemic and mucosal immune responses following intra-nasal (IN)
administration of mice with protection from in vivo vaginal challenge with chlamydiae
compared to ntPE IN immunized mice. While ntPE1 shows considerable promise, we
consider it essential to provide efficacy data on more than just one construct and more
than one route of delivery and dosing schedule to pursue a particular route and vaccine
construct(s) for clinical trials. Thus, the specific aims are to: 1) evaluate humeral and
cell-mediated immune responses to our four vaccine constructs compared to ntPE, and
determine an optimized route (IN, oral, SQ) and dosing schedule; and 2) evaluate
protection from challenge with CT for our constructs compared to ntPE.
Desired Skills or Experience: Undergrad interested in a multidimentional and fulfilling
lab experience – no prior experience required although some courses in molecular and
cell biology would be helpful.
Time Commitment: Full time in summer and then part time during the academic year
for those students interested in continuing; the project could become a senior thesis.
Preferred Starting Date: Late May
__________________________
4.) PROJECT NAME: Genomics of respiratory pathogens of biodefense importance.
General Topic (keywords): Chlamydia psittaci, Chlamydia trachomatis, Chlamydia
pneumoniae,
Legionella
pneumophila,
Mycoplasma pneumonia, genomics,
pathogenesis
Project Description(s): There is an urgent need to develop rapid sample-to-answer
clinic and field deployable diagnostics for NIAID Category A, B and C biothreat
pathogens to protect both military and civilian populations. The goal of this proposal is to
advance and validate a lead candidate diagnostic—a novel microfluidics nucleic acid
detection and sequencing diagnostic platform—to identify Category B pathogen
Chlamydia psittaci (Cps) that causes life-threatening respiratory diseases and has
historically been a focus of bioweapons development as well as being a vastly
understudied pathogen. We will also detect emerging Cps pathogens and non-biothreat
pathogens that are the leading cause of atypical pneumonia and often confused with
biothreat agents in clinical presentation: Chlamydia trachomatis (Ct), Chlamydia
pneumoniae (Cpn), Mycoplasma pneumoniae (Mp) and Legionella pneumophila (Lp).
There are currently few or no commercial diagnostics for these pathogens in the US.
The Aims are to: 1) genome sequence representative Cps biothreat and non-biothreat
atypical respiratory pathogens for robust primer selection; 2) employ the primer selection
pipeline developed by Dr. Read to identify primers based on comparative genomics of
available genomes and those sequenced in Aim 1 for differentiating biothreat and nonbiothreat atypical respiratory pathogens, and develop a multiplexed assay for DNA
amplification to distinguish each pathogen; and 3) evaluate the sensitivity, specificity and
positive and negative predictive value of the assay using first spiked samples and then
clinical NP swabs and sputum samples compared to the available commercial nucleic
acid amplification tests for Ct, Cpn, Mp and Lp (none exist for Cps), and compared to
highly sensitive in-house RT-PCR assays. A broadly used diagnostic will detect patients
with common but also biothreat infection, enabling early identification of an attack and
rapid treatment of infected military and civilian populations.
Desired Skills or Experience: Undergrad interested in a multidimentional and fulfilling
lab experience – no prior experience required although some courses in molecular
biology and/or genetics would be helpful.
Time Commitment: Full time in summer and then part time during the academic year
for those students interested in continuing; the project could become a senior thesis.
Preferred Starting Date: Late May