Bio


Dr. Jamie Imam received her Bachelors degree in Biological Sciences and Psychology from Carnegie Mellon University and her Ph.D. in Genetics from the Stanford School of Medicine. In addition to teaching, Jamie is the Coordinator of the Honors Program in Biology. When she is not teaching or doing science outreach, she enjoys reading, baking and spending time outdoors with her family.

Academic Appointments


All Publications


  • A high-enrollment course-based undergraduate research experience improves student conceptions of scientific thinking and ability to interpret data. CBE life sciences education Brownell, S. E., Hekmat-Scafe, D. S., Singla, V., Chandler Seawell, P., Conklin Imam, J. F., Eddy, S. L., Stearns, T., Cyert, M. S. 2015; 14 (2)

    Abstract

    We present an innovative course-based undergraduate research experience curriculum focused on the characterization of single point mutations in p53, a tumor suppressor gene that is mutated in more than 50% of human cancers. This course is required of all introductory biology students, so all biology majors engage in a research project as part of their training. Using a set of open-ended written prompts, we found that the course shifts student conceptions of what it means to think like a scientist from novice to more expert-like. Students at the end of the course identified experimental repetition, data analysis, and collaboration as important elements of thinking like a scientist. Course exams revealed that students showed gains in their ability to analyze and interpret data. These data indicate that this course-embedded research experience has a positive impact on the development of students' conceptions and practice of scientific thinking.

    View details for DOI 10.1187/cbe.14-05-0092

    View details for PubMedID 26033869

  • The RB family is required for the self-renewal and survival of human embryonic stem cells NATURE COMMUNICATIONS Conklin, J. F., Baker, J., Sage, J. 2012; 3

    Abstract

    The mechanisms ensuring the long-term self-renewal of human embryonic stem cells are still only partly understood, limiting their use in cellular therapies. Here we found that increased activity of the RB cell cycle inhibitor in human embryonic stem cells induces cell cycle arrest, differentiation and cell death. Conversely, inactivation of the entire RB family (RB, p107 and p130) in human embryonic stem cells triggers G2/M arrest and cell death through functional activation of the p53 pathway and the cell cycle inhibitor p21. Differences in E2F target gene activation upon loss of RB family function between human embryonic stem cells, mouse embryonic stem cells and human fibroblasts underscore key differences in the cell cycle regulatory networks of human embryonic stem cells. Finally, loss of RB family function promotes genomic instability in both human and mouse embryonic stem cells, uncoupling cell cycle defects from chromosomal instability. These experiments indicate that a homeostatic level of RB activity is essential for the self-renewal and the survival of human embryonic stem cells.

    View details for DOI 10.1038/ncomms2254

    View details for Web of Science ID 000316356700012

    View details for PubMedID 23212373

  • Using Yeast to Determine the Functional Consequences of Mutations in the Human p53 Tumor Suppressor Gene: An Introductory Course-Based Undergraduate Research Experience in Molecular and Cell Biology BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Hekmat-Scafe, D. S., Brownell, S. E., Seawell, P. C., Malladi, S., Imam, J. F., Singla, V., Bradon, N., Cyert, M. S., Stearns, T. 2017; 45 (2): 161-178

    View details for DOI 10.1002/bmb.21024

    View details for Web of Science ID 000398045000010

  • Neat1 is a p53-inducible lincRNA essential for transformation suppression. Genes & development Mello, S. S., Sinow, C., Raj, N., Mazur, P. K., Bieging-Rolett, K., Broz, D. K., Imam, J. F., Vogel, H., Wood, L. D., Sage, J., Hirose, T., Nakagawa, S., Rinn, J., Attardi, L. D. 2017; 31 (11): 1095–1108

    Abstract

    The p53 gene is mutated in over half of all cancers, reflecting its critical role as a tumor suppressor. Although p53 is a transcriptional activator that induces myriad target genes, those p53-inducible genes most critical for tumor suppression remain elusive. Here, we leveraged p53 ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) and RNA-seq (RNA sequencing) data sets to identify new p53 target genes, focusing on the noncoding genome. We identify Neat1, a noncoding RNA (ncRNA) constituent of paraspeckles, as a p53 target gene broadly induced by mouse and human p53 in different cell types and by diverse stress signals. Using fibroblasts derived from Neat1(-/-) mice, we examined the functional role of Neat1 in the p53 pathway. We found that Neat1 is dispensable for cell cycle arrest and apoptosis in response to genotoxic stress. In sharp contrast, Neat1 plays a crucial role in suppressing transformation in response to oncogenic signals. Neat1 deficiency enhances transformation in oncogene-expressing fibroblasts and promotes the development of premalignant pancreatic intraepithelial neoplasias (PanINs) and cystic lesions in Kras(G12D)-expressing mice. Neat1 loss provokes global changes in gene expression, suggesting a mechanism by which its deficiency promotes neoplasia. Collectively, these findings identify Neat1 as a p53-regulated large intergenic ncRNA (lincRNA) with a key role in suppressing transformation and cancer initiation, providing fundamental new insight into p53-mediated tumor suppression.

    View details for DOI 10.1101/gad.284661.116

    View details for PubMedID 28698299

    View details for PubMedCentralID PMC5538433

  • A High-Enrollment Course-Based Undergraduate Research Experience Improves Student Conceptions of Scientific Thinking and Ability to Interpret Data CBE-LIFE SCIENCES EDUCATION Brownell, S. E., Hekmat-Scafe, D. S., Singla, V., Seawell, P. C., Imam, J. F., Eddy, S. L., Stearns, T., Cyert, M. S. 2015; 14 (2)

    View details for DOI 10.1187/cbe.14-05-0092

    View details for Web of Science ID 000355555900011

    View details for PubMedID 26033869

  • A crucial requirement for Hedgehog signaling in small cell lung cancer NATURE MEDICINE Park, K., Martelotto, L. G., Peifer, M., Sos, M. L., Karnezis, A. N., Mahjoub, M. R., Bernard, K., Conklin, J. F., Szczepny, A., Yuan, J., Guo, R., Ospina, B., Falzon, J., Bennett, S., Brown, T. J., Markovic, A., Devereux, W. L., Ocasio, C. A., Chen, J. K., Stearns, T., Thomas, R. K., Dorsch, M., Buonamici, S., Watkins, D. N., Peacock, C. D., Sage, J. 2011; 17 (11): 1504-U1506

    Abstract

    Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer for which there is no effective treatment. Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment. Constitutive activation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCLC in vitro and the initiation and progression of mouse SCLC in vivo. Reciprocally, deletion of Smo in Rb1 and Trp53-mutant lung epithelial cells strongly suppressed SCLC initiation and progression in mice. Furthermore, pharmacological blockade of Hedgehog signaling inhibited the growth of mouse and human SCLC, most notably following chemotherapy. These findings show a crucial cell-intrinsic role for Hedgehog signaling in the development and maintenance of SCLC and identify Hedgehog pathway inhibition as a therapeutic strategy to slow the progression of disease and delay cancer recurrence in individuals with SCLC.

    View details for DOI 10.1038/nm.2473

    View details for Web of Science ID 000296779300043

    View details for PubMedID 21983857

    View details for PubMedCentralID PMC3380617

  • Loss of p130 Accelerates Tumor Development in a Mouse Model for Human Small-Cell Lung Carcinoma CANCER RESEARCH Schaffer, B. E., Park, K., Yiu, G., Conklin, J. F., Lin, C., Burkhart, D. L., Karnezis, A. N., Sweet-Cordero, E. A., Sage, J. 2010; 70 (10): 3877-3883

    Abstract

    Small-cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer. Although SCLC patients often initially respond to therapy, tumors nearly always recur, resulting in a 5-year survival rate of less than 10%. A mouse model has been developed based on the fact that the RB and p53 tumor suppressor genes are mutated in more than 90% of human SCLCs. Emerging evidence in patients and mouse models suggests that p130, a gene related to RB, may act as a tumor suppressor in SCLC cells. To test this idea, we used conditional mutant mice to delete p130 in combination with Rb and p53 in adult lung epithelial cells. We found that loss of p130 resulted in increased proliferation and significant acceleration of SCLC development in this triple-knockout mouse model. The histopathologic features of the triple-mutant mouse tumors closely resembled that of human SCLC. Genome-wide expression profiling experiments further showed that Rb/p53/p130-mutant mouse tumors were similar to human SCLC. These findings indicate that p130 plays a key tumor suppressor role in SCLC. Rb/p53/p130-mutant mice provide a novel preclinical mouse model to identify novel therapeutic targets against SCLC.

    View details for DOI 10.1158/0008-5472.CAN-09-4228

    View details for Web of Science ID 000278486300004

    View details for PubMedID 20406986

  • Keeping an Eye on Retinoblastoma Control of Human Embryonic Stem Cells JOURNAL OF CELLULAR BIOCHEMISTRY Conklin, J. F., Sage, J. 2009; 108 (5): 1023-1030

    Abstract

    Human embryonic stem cells (hESCs) hold great promise in regenerative medicine. However, before the full potential of these cells is achieved, major basic biological questions need to be addressed. In particular, there are still gaps in our knowledge of the molecular mechanisms underlying the derivation of hESCs from blastocysts, the regulation of the undifferentiated, pluripotent state, and the control of differentiation into specific lineages. Furthermore, we still do not fully understand the tumorigenic potential of hESCs, limiting their use in regenerative medicine. The RB pathway is a key signaling module that controls cellular proliferation, cell survival, chromatin structure, and cellular differentiation in mammalian cells. Members of the RB pathway are important regulators of hESC biology and manipulation of the activity of this pathway may provide novel means to control the fate of hESCs. Here we review what is known about the expression and function of members of the RB pathway in hESCs and discuss areas of interest in this field.

    View details for DOI 10.1002/jcb.22342

    View details for Web of Science ID 000272640900001

    View details for PubMedID 19760644

  • Stabilization and analysis of intron lariats in vivo METHODS Conklin, J. F., Goldman, A., Lopez, A. J. 2005; 37 (4): 368-375

    Abstract

    The analysis of lariats produced in vivo during pre-mRNA splicing is a powerful tool for elucidation of regulatory mechanisms and identification of natural recursive splicing events. Nevertheless, this analysis is technically challenging because lariats normally have short half-lives. With appropriate controls, RT-PCR amplification and sequencing of the region spanning the 2'-5' phosophodiester bond at the branch junction can be a sensitive and versatile method for lariat analysis. This approach can be facilitated and enhanced by reducing the activity of debranching enzyme (DBR) in order to stabilize lariats. We have generated a set of plasmids for dsRNA-mediated knockdown of DBR under diverse conditions in transgenic Drosophila and in cultured cells. We describe the use of these plasmids and protocols for lariat analysis. We have generated transgenic Drosophila strains carrying a GAL4-regulated RNAi construct that allows selective knockdown of DBR in specific tissues or developmental stages, using the large collection of available GAL4 expression lines. These strains should prove useful for detailed developmental analyses of alternative and recursive splicing and for genetic analyses of splicing factors. Similar approaches should be readily adaptable to other organisms.

    View details for DOI 10.1016/j.ymeth.2005.08.002

    View details for Web of Science ID 000234035800010

    View details for PubMedID 16314266

  • Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements GENETICS Burnette, J. M., Miyamoto-Sato, E., Schaub, M. A., Conklin, J., Lopez, A. J. 2005; 170 (2): 661-674

    Abstract

    Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated. We present bioinformatic, phylogenetic, and experimental evidence in Drosophila for a mechanism that subdivides many large introns by recursive splicing at nonexonic elements and alternative exons. Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns >20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns <10 kb. The predicted sites in long introns are highly conserved between Drosophila melanogaster and Drosophila pseudoobscura, despite extensive divergence of other sequences within the same introns. These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns. Experimental analyses of in vivo processing intermediates and lariat products from four large introns in the unrelated genes kuzbanian, outspread, and Ultrabithorax confirmed that these introns are removed by a series of recursive splicing steps using the predicted nonexonic sites. Mutation of nonexonic site RP3 within Ultrabithorax also confirmed that recursive splicing is the predominant processing pathway even with a shortened version of the intron. We discuss currently known and potential roles for recursive splicing.

    View details for DOI 10.1534/genetics.104.039701

    View details for Web of Science ID 000230441900016

    View details for PubMedID 15802507