Perelman School of Medicine at the University of Pennsylvania

Topics in Molecular Medicine

Course Outline

Fall 2023


TiMM is planned as a once-weekly seminar course whose goal is to introduce students to the ways in which biomedical research can provide new insights into clinical medicine and, conversely, how knowledge of clinical disease impacts scientific discovery. Due to space limitations, the course is open only to 1st year Combined Degree (MD/PhD) students. The course will meet for 90 minutes each week. The first class will meet on Friday, September 8.

The course will be in a seminar style. Four or five students will be assigned to present at each session. Each session has a different faculty member as a preceptor; this faculty member, in consultation with the course directors, has typically chosen one state-of-the-art research paper that provides cellular and/or molecular insight into a topic of clinical relevance. At least one of the sessions will also focus not on molecular medicine, but on how social science research impacts the practice of medicine. For all of the sessions, the faculty member will meet with the students before the class session to provide additional insight into the topic. The team will present the clinical background of the problem, the scientific background for the paper, critically dissect the data and interpretations in the scientific paper, and discuss its implications. All of the students in the class will be expected to have read the research paper, to contribute a question for discussion, and to participate in the class discussion. Topics assignments for the semester will be made well in advance of the first class.

Objectives, Grading and Class Participation

TiMM is structured to provide you with the experience of learning about an area of clinical medicine and reading state-of-the-art papers in a related discipline of basic science. Creating connections between scientific advances and clinical need is something that you, as physician-scientists, will do for the remainder of your career, and is one of the reasons this course has been popular with the students who take it as well as the faculty who participate as instructors. Each student will help lead two group presentations, but every student will actively participate in every session. The success of the class depends on you – in particular, on the quality of the discussion. As a graduate school course, the course will be graded on a letter grade scale. Half of your grade will reflect your participation across sessions, and half will depend on the two presentations. The marker of participation in regular session will be the quality (not quantity) of your comments and the quality of your submitted discussion topic or question for each session. To make the sessions interactive, we expect you to have read the papers and thought about the topic before each class. This class is different from other courses during your first year – it challenges you to read papers criticallydesign thought experiments, and generate hypotheses that (if you do your job well) no one in the class will have thought of before. We should also note that you should let us know in advance if you will need to miss a class. While we expect attendance at every class, more than one absence will require additional work to account for the lack of participation.

Presenting in TiMM

Below is an outline of how to approach a TiMM presentation.  You and the other member(s) of your group should plan to meet as a group with your preceptor twice, the first time at least two weeks before the presentation. It is your responsibility to contact the preceptor to find times to meet. Note that your preceptors are busy and scheduling should be done early. Although each member of the group is responsible for covering a specific part of the topic, you should work as a team: the best sessions come from groups that coordinate their presentations. It is critical that the components be well integrated and teams should strive to avoid redundancy in the presentations. Since time is limited, each group should have a well-organized plan for presentation in order to maximize their ability to effectively convey the major discussion points and targeted discussion points. Once you have a presentation prepared, try to practice it a few times with your partners and (even better) in front of colleagues who are unfamiliar with the material. The goal of your presentation is to stimulate discussion on the part of your colleagues, who will all have read and thought about the assigned paper and will be coming up with their own questions (below). You should also pose questions directly to the class in a manner than can stimulate discussion.

Clinical Background - (Plan for 10-15 minutes)

Outline for presentation
We encourage you to consider inclusion of a case study as part of your clinical presentation. This can help the members of the class better “visualize” the disease. Your preceptor will be invaluable in helping you prepare a case and highlight the essential features of the disease. Keep in mind that it’s not necessary to be exhaustive – one of the most effective case presentations given in this class was a graph of Lou Gehrig’s batting average to illustrate the effects of ALS. You should convey enough of the clinical background to allow for everyone to understand the motivation of the work or its implications, but not aim to recapitulate what you would hear in a full clinical lecture on the topics. Your classmates will be encouraged not to ask any questions during the background to allow you to efficiently move to the science.

Define the disease in one or two sentences.  For example: myocardial infarction results from the formation of thrombi in the coronary arteries at sites of atherosclerosis leading to secondary death of heart muscle.

In two or three sentences, introduce the importance of this disease by discussing the Who, Where, and When of the disease.  Some diseases will be rare, others will be common.

Clinical presentation and diagnosis
For TiMM purposes, keep this lean and mean.  Briefly tell us how people with this disease present: what do they complain about (i.e. symptoms), what is found on physical examination, what are the clinical laboratory findings? For genetic diseases, is there a screen that can be performed in utero or on potential carriers?  Be brief and don’t worry about mentioning everything.

Clinical treatment and prognosis
What is the current treatment and how effective is it? What is the long-term outlook for individuals with this disease?  Again, don’t be exhaustive.  The idea is to discuss how effective modern medicine is in treating and preventing the disease. Try to focus your clinical presentation anticipating the associated research papers.

This will likely segue into the research paper.  Briefly summarize what is believed to underlie the disease process at the cellular and molecular level.  Be very specific and limit your discussion to one slide related specifically to the disease.  Summarize the outstanding questions that need to be answered to understand this disease at a basic level.

While your classmates will be encouraged to not interrupt during the initial background, at this point you can open up to questions related to the clinical disease before moving on to the science.

Science Presentation - (Plan for 30 minutes)

It will be up to each group to decide how to divide the time in these didactic presentations. However, keep in mind that it is crucial that you be strategic and selective in your presentations. (We should note that there are various ways of dividing these presentations up – in addition to discussing the major findings, one presenter may wish to go into details regarding technique – i.e. giving a particular functional “activity,” how could one clone “the gene?” Importantly, though, these should be points that would not be encountered in a standard medical school class.)

Some areas to think about covering as you are organizing the presentations include:

These papers have been chosen because they represent the state of the art, thus the goal of this part of the presentation is not to critique the papers as in a journal club but rather to focus on explaining the research from a broad perspective. Why were the authors interested in a particular question, how did they choose to answer it, what did they learn? The idea behind this part of the session (and indeed the whole course) is explore the link between a clinical question (which may be centuries old) and the scientific approach to an answer (which is often based on a method or data available for less than a few years). What is the question? What aspect of a disease that is not understood is being addressed?  Be specific and state this in one or two sentences.  The importance of this question should be clear after hearing the clinical overview. Of note, it is OK to call on your classmates; this can be an effective way of achieving active participation!

The scientific presentation requires solidly establishing the background before moving into the main scientific paper. Your classmates will not have read the key literature that preceded this current paper, so your first task will be to introduce them to what was known prior to the paper. Your goal is to make clear the state of the field prior to this paper.  Don’t be exhaustive; use the details that pertain to this paper only.  Try to make it simple, even if it isn’t!  We can hammer out the important details together during discussion. Most selected papers will have some background in the introduction or in accompanying editorials (e.g. news and views) to help you here but you will likely need a review paper and need to read some of the key background primary literature.  Ask your preceptor for guidance.

The Approach
How was the experiment designed and why?  Sometimes the findings are fortuitous, but most scientific discovery is planned.  Briefly outline the approach to the question.  Don’t talk about standard scientific techniques but do elaborate on the use of a new method if you feel it was crucial to the success of the investigators. Keep in mind that one of your colleagues may have already discussed a key method in detail. If a paper draws on methods that have been discussed in an earlier session of TiMM, you should feel comfortable building on that prior discussion and try to avoid redundancy in reviewing basic methods. You should use this as an opportunity to critically dissect the approach also. What were the strengths or shortcomings of the approach? What might have been done differently? 

If there is a method utilized in the paper that requires special attention, one of the presenters should take the opportunity to discuss the method (see above). Ideally, a method discussion may be included for an approach that has fairly broad application but is not widely understood and would benefit from a detailed explanation. Questions to address during a method presentation: What is the method in practical terms: how is it performed, what does it measure? How is this method applied scientifically? Are there complementary methods that might be used to confirm or test results obtained using this approach?


Fostering Discussion - (Plan for presenting 5-10 minutes, then discussing for 25-30 minutes)

The formal presentations should be done at the end of one hour. Having analyzed the paper in great detail, now is your opportunity to echo back to the overall motivation for the paper. What is the impact of the paper on the clinical case? Often there will be papers that cite this work after its publication or a controversy that gets stirred up. What were the downstream implications for science in that case?

The major goal of TiMM is to move beyond the rote learning of a clinical presentation and journal club to stimulate students to think as physician scientists. The last section fostering discussion should naturally transition into a more general discussion. What is the next important question? What technical hurdles need to be overcome, and how might I do that? What other techniques or fields of research could be brought to bear on the problem?

At this point in the discussion, the presenters will also lean upon the questions that have been submitted by their classmates to foster discussion (see below). While the presentation is ongoing, later presenters in the group can take time to select from among the questions, introduce those questions and facilitate open discussion. It is expected that everyone will participate in the discussion. Broad class participation is essential to the educational mission of this class. Your preceptor will be present during your presentation and can be thought of as a resource to weigh in on the important discussion questions. Raj and Rahul may also help raise important discussion points. However, you should try to lead to discussion and extract as much as possible from your classmates. The best presentations naturally foster a high level of engagement from your fellow students by stimulating them to think and contribute. We will attempt to end class on time (class is 90 minutes long). Note that the last 5 min of class is reserved for your preceptors to share more about themselves, why they selected this paper, and any big picture advice they have as you set upon the pathway towards becoming a physician-scientist.

Discussion Questions

After reading the key scientific paper, all students who are not presenting will be required to submit one question (only) for discussion. These questions will be written out with the student’s name and turned in when arriving to class. Ideally, these should be short, simple, and thought provoking.  The discussion organizer will flip through the questions and organize them in the order that they think is best fit for fostering discussion. Although other questions may organically arise from the presentation, these questions can serve as the basis for the discussion in the last section of class. Note that if preferred the presenters can request their classmates to email questions in advance of the class, rather than having them written upon arrival to the class.


If you have symptoms that could be COVID-19, please do not come to class in person. If you do notice symptoms, please take the following steps:

1.  Utilize the resources on Penn's COVID-19 Response to schedule a COVID test.

2.  Report your symptoms on PennOpen Pass.

3.  Email Rajan Jain, Rahul Kohli and Hope Charney about your pending test as soon as possible so that we can plan for your possible absence. 

4.  If your test result is positive, please refer to the University's care and contact tracing teams for instructions on when you can return to class. 

5.  If your test result is negative, we ask that you do not come to class if still experiencing any upper respiratory symptoms. 

6.  If you need to participate remotely, we will provide a Zoom link that will enable you to join the hybrid lesson. (Provided that you feel well enough to do so)


Feedback on your presentation will come in several forms. The course directors and session preceptors will provide you with verbal feedback at the end of your presentation. Additionally, you will each be asked to anonymously provide written feedback on one group's presentation during the semester. Both of these feedback forums will focus on the clarity and organization of the presentation, along with your group's ability to guide and direct the discussion.

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